Lung Cancer

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I recently met Jane, a 53-year-old woman with metastatic breast cancer. She was referred to me by the breast oncology team, which routinely refers all metastatic patients to our palliative care clinic.

Clocking in at under 20 minutes, my consultation with Jane might have been one of my shortest on record. Not only had the breast oncology team already addressed Jane’s symptoms, which mainly consisted of hot flashes and joint pain attributable to treatment with an aromatase inhibitor, but they had already started planning ahead for the future of her illness. Jane had completed an advance directive and had a realistic and hopeful perspective on how her illness would progress. She understood the goal of her treatment was to “keep the cancer asleep,” as she put it, and she was very clear about her own goals: to live long enough to see her granddaughter graduate from high school in 2 years and to take a long-awaited trip to Australia later in 2023.

There wasn’t much for me to do. In fact, I daresay that Jane really did not need to see a palliative care specialist because the primary palliative care she was receiving from the breast oncology team was superb. Jane was receiving excellent symptom management from a nurse practitioner and oncologist, plus a social worker provided her with coping strategies. She was already having conversations with her primary medical team and her family about what to expect in the future and how to plan ahead for all possible outcomes.
 

When should a patient be referred to palliative care?

Integrating palliative care into routine oncologic care need not always require the time and skill of a palliative care team for every patient. Oncology providers can provide basic palliative care services without consulting a palliative care specialist.

For example, if a primary care doctor tried to refer every patient with hypertension to cardiology, the cardiologist would probably say that primary care should be able to handle basic hypertension management. In my experience from working in an oncology clinic for the past 9 years, I’ve found that oncology providers don’t need to refer every advanced cancer patient to our palliative care program. Most oncologists have good communication skills and are more than capable of managing symptoms for patients.

But don’t get me wrong. I’m not discouraging referrals to palliative care, instead I’m suggesting the careful triage of patients.
 

Palliative care for all?

In 2010, Jennifer S. Temel MD, published a landmark study in the New England Journal of Medicine that demonstrated significant improvements in quality of life and mood in patients with metastatic lung cancer who received concurrent palliative care. After the study was published many voices inside oncology and palliative care began to advocate for a “palliative care for all” approach to patients with metastatic disease. But this is often interpreted as “specialty palliative care for all,” rather than its original intended meaning that all patients with metastatic disease receive the essential elements of palliative care (biopsychosocial symptom support and conversations about goals of care) either through their primary oncology teams or, if needed, specialty palliative care teams.

The fact is that most specialty palliative care clinics do not have the manpower to meet the needs of all patients with advanced cancers, much less all patients living with serious illness. A main goal of integrating palliative care into routine outpatient health care has always been (and in my opinion, should continue to be) to enhance the primary palliative care skills of specialists, such as oncologists and cardiologists, who care for some of our sickest patients.

This could take many forms. For one, it can be helpful to screen patients for palliative care needs. The American College of Surgeons Commission on Cancer mandates distress screening for all patients as a condition of accreditation. Distress screening using a validated tool such as the National Comprehensive Cancer Network Distress Thermometer can differentiate patients who have minimal distress and may not need much additional support beyond what is provided by their oncology team from those whose distress feels unmanageable and overwhelming.

In terms of primary palliative care symptom management, most oncology teams I work with are comfortable prescribing basic medications for pain, nausea, constipation, and anxiety. They’re also comfortable referring oncology patients for nutrition needs while undergoing chemotherapy as well as to social work and spiritual care for emotional support and counseling.

Oncology teams should continually work on communications skills. They should use “Ask, Tell, Ask” to elicit prognostic awareness, convey critical information, and assess for recall and understanding at pivotal points in the cancer journey, such as when the disease progresses or the patient’s clinical condition changes. They should practice a normalizing script they can use to introduce advance care planning to their patients in the first few visits. When I meet with a patient for the first time, I usually begin by asking if they have prepared an advanced directive. If not, I ask if they’ve thought about who will make medical decisions for them should the need arise. If the patient has documented in writing their preference for care in an emergency situation, I ask for a copy for their chart.
 

When should patients be referred to a specialty palliative care program?

I tell our oncology teams to involve me after they have tried to intervene, but unsuccessfully because of the patient having intractable symptoms, such as pain, or the disease is not responding to treatments. Or, because there are significant communication or health literacy barriers. Or, because there are challenging family dynamics that are impeding progress in establishing goals of care.

A physician should refer to specialty palliative care when there are multiple comorbid conditions that impact a patient’s prognosis and ability to tolerate treatments. These patients will need detailed symptom management and nuanced conversations about the delicate balance of maintaining quality of life and trying to address their malignancy while also avoiding treatments that may do more harm than good.

At the end of the day, all patients with serious illnesses deserve a palliative care approach to their care from all of their clinicians, not just from the palliative care team. By continuously honing and implementing primary palliative care skills, oncology teams can feel empowered to meet the needs of their patients themselves, strengthening their bond with their patients making truly patient-centered care much more likely.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

“Do you smoke?” I asked the patient.

“Yes, and I got what I deserved,” he answered, clearly upset.

I ignored his reaction and continued with the exam, but in retrospect, I should have explained why doctors ask patients this question.

It was not my intention to be rude or blame the patient for his lung cancer diagnosis. Doctors ask patients if they smoke because a smoking history can change the type of treatment and it can be associated with other conditions that may interfere with treatment. It can also determine whether smoking cessation assistance should be offered to the patient. It is crucial that we as doctors know a patient’s medical history, but how we approach sensitive issues may determine if we even get the information we need. In this case, I didn’t explain why I asked the patient if he smoked. Had I taken the time to explain why I needed to know if and how long he smoked and that I was not blaming him for his lung cancer diagnosis, we may have had a more mutually respectful and beneficial relationship.

Almost all of my patients with lung cancer have been asked at one time or another – by a health care provider, friends, or acquaintances – “Do you smoke?” Whether or not they smoked, patients with lung cancer feel the weight of moral judgment being cast upon them by society.

It is common for people who smoke and who go on to develop lung cancer to be weighed down by guilt associated with their diagnosis. Patients with lung cancer face stigma-associated hurdles based on the “I did it to myself” mindset. This societal stigma is not without harm as it can result in emotional responses of guilt and self-blame. This internalized stigma may lead to psychosocial distress and decreased interactions with family, friends, and health care providers. The guilt may drive a patient to forgo lung cancer screening, minimize symptoms, delay seeking treatment, and not advocate for themselves with their physician. Some patients even decide to forgo all treatment.

What about patients who never smoked? They too feel tinged with blame. Many of these patients feel called upon to defend themselves by proclaiming loudly that they have never smoked.

Blame and shame also divides the lung cancer community, resulting in less advocacy. It may also impact research dollars for lung cancer. According to the Lung Cancer Research Foundation, “Despite being the leading cause of cancer mortality, lung cancer receives far less research funding than any other cancer.” By comparison, women with breast cancer are showered with far more resources, supportive services, fundraising events, and certainly more lobbying.

By making unintentional hurtful statements and using judgmental or denigrating language, the lung cancer community may unconsciously be playing a role in perpetuating stigmas associated with lung cancer. That kind of language can come across as blame.

The International Association for the Study of Lung Cancer has developed a language guide to help reduce stigma associated with lung cancer. The aim is to reduce and replace traditional medical language during our patient interactions, presentations, and publications with language that is more empathic and nonjudgmental.

For example, replace the term “cancer patient” with the term “the patient with cancer.” The patient is a person who happens to have been diagnosed with lung cancer, they are not “cancer.” Patients can be very sensitive to language and may misinterpret language that doctors commonly use. Language such as “the patient failed treatment” may be interpreted by patients as a personal failure. In reality, the treatment failed the patient, instead of the other way around. Instead, shift the blame from the patient to the cancer. Adopt terms like “the tumor did not respond to treatment.” Or, “the cancer progressed” instead of “the patient progressed.”

Language around smoking is particularly stigmatizing because it categorizes a person by a behavior. As health care providers, we should consider removing the term “smoker” from our interactions with patients and instead, use “patient who smokes” or ”patient with a smoking history.” Other ways health care providers can reduce stigma triggered by assessing smoking status include using supportive communication skills, providing a rationale for asking smoking related questions, offering help and tobacco cessation and other resources, and displaying empathic behavior, such as maintaining eye contact and a nonjudgmental body position orientated toward the patient.

Many of these common medical phrases were developed to enable efficient communication among health care professionals. Times have changed and patients should not be defined by an illness. They are people first. In addition to improving patient interactions in clinic, using nonjudgmental language whenever possible in presentations and publications is also extremely important, as patients are living longer and getting more involved in research and advocacy.

“Words have energy and power with the ability to help, to heal, to hinder, to hurt, to harm, to humiliate, and to humble,” says Yehuda Berg, author and codirector of the Kabbalah Centre International in Los Angeles.
 

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

“Do you smoke?” I asked the patient.

“Yes, and I got what I deserved,” he answered, clearly upset.

I ignored his reaction and continued with the exam, but in retrospect, I should have explained why doctors ask patients this question.

It was not my intention to be rude or blame the patient for his lung cancer diagnosis. Doctors ask patients if they smoke because a smoking history can change the type of treatment and it can be associated with other conditions that may interfere with treatment. It can also determine whether smoking cessation assistance should be offered to the patient. It is crucial that we as doctors know a patient’s medical history, but how we approach sensitive issues may determine if we even get the information we need. In this case, I didn’t explain why I asked the patient if he smoked. Had I taken the time to explain why I needed to know if and how long he smoked and that I was not blaming him for his lung cancer diagnosis, we may have had a more mutually respectful and beneficial relationship.

Almost all of my patients with lung cancer have been asked at one time or another – by a health care provider, friends, or acquaintances – “Do you smoke?” Whether or not they smoked, patients with lung cancer feel the weight of moral judgment being cast upon them by society.

It is common for people who smoke and who go on to develop lung cancer to be weighed down by guilt associated with their diagnosis. Patients with lung cancer face stigma-associated hurdles based on the “I did it to myself” mindset. This societal stigma is not without harm as it can result in emotional responses of guilt and self-blame. This internalized stigma may lead to psychosocial distress and decreased interactions with family, friends, and health care providers. The guilt may drive a patient to forgo lung cancer screening, minimize symptoms, delay seeking treatment, and not advocate for themselves with their physician. Some patients even decide to forgo all treatment.

What about patients who never smoked? They too feel tinged with blame. Many of these patients feel called upon to defend themselves by proclaiming loudly that they have never smoked.

Blame and shame also divides the lung cancer community, resulting in less advocacy. It may also impact research dollars for lung cancer. According to the Lung Cancer Research Foundation, “Despite being the leading cause of cancer mortality, lung cancer receives far less research funding than any other cancer.” By comparison, women with breast cancer are showered with far more resources, supportive services, fundraising events, and certainly more lobbying.

By making unintentional hurtful statements and using judgmental or denigrating language, the lung cancer community may unconsciously be playing a role in perpetuating stigmas associated with lung cancer. That kind of language can come across as blame.

The International Association for the Study of Lung Cancer has developed a language guide to help reduce stigma associated with lung cancer. The aim is to reduce and replace traditional medical language during our patient interactions, presentations, and publications with language that is more empathic and nonjudgmental.

For example, replace the term “cancer patient” with the term “the patient with cancer.” The patient is a person who happens to have been diagnosed with lung cancer, they are not “cancer.” Patients can be very sensitive to language and may misinterpret language that doctors commonly use. Language such as “the patient failed treatment” may be interpreted by patients as a personal failure. In reality, the treatment failed the patient, instead of the other way around. Instead, shift the blame from the patient to the cancer. Adopt terms like “the tumor did not respond to treatment.” Or, “the cancer progressed” instead of “the patient progressed.”

Language around smoking is particularly stigmatizing because it categorizes a person by a behavior. As health care providers, we should consider removing the term “smoker” from our interactions with patients and instead, use “patient who smokes” or ”patient with a smoking history.” Other ways health care providers can reduce stigma triggered by assessing smoking status include using supportive communication skills, providing a rationale for asking smoking related questions, offering help and tobacco cessation and other resources, and displaying empathic behavior, such as maintaining eye contact and a nonjudgmental body position orientated toward the patient.

Many of these common medical phrases were developed to enable efficient communication among health care professionals. Times have changed and patients should not be defined by an illness. They are people first. In addition to improving patient interactions in clinic, using nonjudgmental language whenever possible in presentations and publications is also extremely important, as patients are living longer and getting more involved in research and advocacy.

“Words have energy and power with the ability to help, to heal, to hinder, to hurt, to harm, to humiliate, and to humble,” says Yehuda Berg, author and codirector of the Kabbalah Centre International in Los Angeles.
 

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

“Do you smoke?” I asked the patient.

“Yes, and I got what I deserved,” he answered, clearly upset.

I ignored his reaction and continued with the exam, but in retrospect, I should have explained why doctors ask patients this question.

It was not my intention to be rude or blame the patient for his lung cancer diagnosis. Doctors ask patients if they smoke because a smoking history can change the type of treatment and it can be associated with other conditions that may interfere with treatment. It can also determine whether smoking cessation assistance should be offered to the patient. It is crucial that we as doctors know a patient’s medical history, but how we approach sensitive issues may determine if we even get the information we need. In this case, I didn’t explain why I asked the patient if he smoked. Had I taken the time to explain why I needed to know if and how long he smoked and that I was not blaming him for his lung cancer diagnosis, we may have had a more mutually respectful and beneficial relationship.

Almost all of my patients with lung cancer have been asked at one time or another – by a health care provider, friends, or acquaintances – “Do you smoke?” Whether or not they smoked, patients with lung cancer feel the weight of moral judgment being cast upon them by society.

It is common for people who smoke and who go on to develop lung cancer to be weighed down by guilt associated with their diagnosis. Patients with lung cancer face stigma-associated hurdles based on the “I did it to myself” mindset. This societal stigma is not without harm as it can result in emotional responses of guilt and self-blame. This internalized stigma may lead to psychosocial distress and decreased interactions with family, friends, and health care providers. The guilt may drive a patient to forgo lung cancer screening, minimize symptoms, delay seeking treatment, and not advocate for themselves with their physician. Some patients even decide to forgo all treatment.

What about patients who never smoked? They too feel tinged with blame. Many of these patients feel called upon to defend themselves by proclaiming loudly that they have never smoked.

Blame and shame also divides the lung cancer community, resulting in less advocacy. It may also impact research dollars for lung cancer. According to the Lung Cancer Research Foundation, “Despite being the leading cause of cancer mortality, lung cancer receives far less research funding than any other cancer.” By comparison, women with breast cancer are showered with far more resources, supportive services, fundraising events, and certainly more lobbying.

By making unintentional hurtful statements and using judgmental or denigrating language, the lung cancer community may unconsciously be playing a role in perpetuating stigmas associated with lung cancer. That kind of language can come across as blame.

The International Association for the Study of Lung Cancer has developed a language guide to help reduce stigma associated with lung cancer. The aim is to reduce and replace traditional medical language during our patient interactions, presentations, and publications with language that is more empathic and nonjudgmental.

For example, replace the term “cancer patient” with the term “the patient with cancer.” The patient is a person who happens to have been diagnosed with lung cancer, they are not “cancer.” Patients can be very sensitive to language and may misinterpret language that doctors commonly use. Language such as “the patient failed treatment” may be interpreted by patients as a personal failure. In reality, the treatment failed the patient, instead of the other way around. Instead, shift the blame from the patient to the cancer. Adopt terms like “the tumor did not respond to treatment.” Or, “the cancer progressed” instead of “the patient progressed.”

Language around smoking is particularly stigmatizing because it categorizes a person by a behavior. As health care providers, we should consider removing the term “smoker” from our interactions with patients and instead, use “patient who smokes” or ”patient with a smoking history.” Other ways health care providers can reduce stigma triggered by assessing smoking status include using supportive communication skills, providing a rationale for asking smoking related questions, offering help and tobacco cessation and other resources, and displaying empathic behavior, such as maintaining eye contact and a nonjudgmental body position orientated toward the patient.

Many of these common medical phrases were developed to enable efficient communication among health care professionals. Times have changed and patients should not be defined by an illness. They are people first. In addition to improving patient interactions in clinic, using nonjudgmental language whenever possible in presentations and publications is also extremely important, as patients are living longer and getting more involved in research and advocacy.

“Words have energy and power with the ability to help, to heal, to hinder, to hurt, to harm, to humiliate, and to humble,” says Yehuda Berg, author and codirector of the Kabbalah Centre International in Los Angeles.
 

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

It had only been 3 weeks since I first met this patient. She presented with an advanced case of colon cancer, but instead of treatment, we had to have a serious talk about death and dying and the goals of care. She died soon after our talk.

Within the course of 2 weeks I saw another new patient, but this time with pancreatic cancer that metastasized to the liver. “When can we start treatment?” he asked. Like my female patient with colon cancer, he was diagnosed too late as he was already in an incurable stage. He was shocked to learn that his condition was in stage 4, that achieving remission would be difficult and a cure, not likely. Certainly, standard of care treatments and clinical trials offered him hope, but they were unlikely to change the outcome.

We take a course in this – that is, in giving bad news, but every doctor has his or her own approach. Some are so uncomfortable with the talk, they choose avoidance and adopt the “look like you gotta go approach.” Or, the doctor may schedule another treatment or another test with the intention of avoiding end-of-life discussions. Other doctors opt for straight talk: “I think you should get your affairs in order. You’ve got 3 months to live.” These are extreme behaviors I wouldn’t recommend.

In my practice, I sit with my patients and explain the diagnosis. After discussing all options and the advanced stage and diagnosis, it ultimately comes down to “Win or lose, I will be here to take care of you.” Sometimes there is therapy that may help, but either way, the patient understands that death is a real possibility.

I find that people just want to know if there is hope. A different treatment regimen or a clinical trial may (or may not) extend their life. And while we cannot predict outcomes, we can give them hope. You can’t shut down hope. True for some people the cup is always half empty, but most people want to live and are optimistic no matter how small the chances are.

These conversations are very difficult. I don’t like them, but then I don’t avoid them either. Fortunately, patients don’t usually come to my office for the first visit presenting with advanced disease. In the cases I described above, one patient had been experiencing unexplained weight loss, but didn’t share it with a physician. And, for the patient with pancreatic cancer, other than some discomfort in the last couple of weeks, the disease was not associated with other symptoms. But the absence of symptoms should not in any way rule out a malignant disease. A diagnosis should be based on a complete evaluation of signs and symptoms followed by testing.

We’ve got to be able to take the time to listen to our patients during these encounters. We may not spend as much time as we should because we’re so busy now and we’re slaves to EMRs. It helps if we take more time to probe symptoms a little longer, especially in the primary care setting.

It is possible for a patient with cancer to be asymptomatic up until the later stages of the disease. A study published in ESMO Open in 2020 found that fewer than half of patients with stage 4 non–small cell lung cancer have only one or two symptoms at diagnosis regardless of whether the patient was a smoker. In this study only 33% of patients reported having a cough and 25% had chest pain.

A study presented in October at the United European Gastroenterology Week found that of 600 pancreatic cancer cases, 46 of these were not detected by CT or MRI conducted 3-18 months prior to diagnosis. Of the 46 cases, 26% were not picked up by the radiologist and the rest were largely as a result of imaging changes over time. Radiology techniques are good, but they cannot pick up lesions that are too small. And some lesions, particularly in pancreatic cancer, can grow and metastasize rather quickly.

When a patient is diagnosed with advanced disease, it is most often simply because of the nature of the disease. But sometimes patients put off scheduling a doctor visit because of fear of the potential for bad news or fear of the doctor belittling their symptoms. Some tell me they were “just hoping the symptoms would disappear.” Waiting too long to see a doctor is never a good idea because timing is crucial. In many cases, there is a small window of opportunity to treat disease if remission is to be achieved.


Dr. Henry is a practicing clinical oncologist with PennMedicine in Philadelphia where he also serves as Vice Chair of the Department of Medicine at Pennsylvania Hospital.
 

This article was updated 12/7/22.

It had only been 3 weeks since I first met this patient. She presented with an advanced case of colon cancer, but instead of treatment, we had to have a serious talk about death and dying and the goals of care. She died soon after our talk.

Within the course of 2 weeks I saw another new patient, but this time with pancreatic cancer that metastasized to the liver. “When can we start treatment?” he asked. Like my female patient with colon cancer, he was diagnosed too late as he was already in an incurable stage. He was shocked to learn that his condition was in stage 4, that achieving remission would be difficult and a cure, not likely. Certainly, standard of care treatments and clinical trials offered him hope, but they were unlikely to change the outcome.

We take a course in this – that is, in giving bad news, but every doctor has his or her own approach. Some are so uncomfortable with the talk, they choose avoidance and adopt the “look like you gotta go approach.” Or, the doctor may schedule another treatment or another test with the intention of avoiding end-of-life discussions. Other doctors opt for straight talk: “I think you should get your affairs in order. You’ve got 3 months to live.” These are extreme behaviors I wouldn’t recommend.

In my practice, I sit with my patients and explain the diagnosis. After discussing all options and the advanced stage and diagnosis, it ultimately comes down to “Win or lose, I will be here to take care of you.” Sometimes there is therapy that may help, but either way, the patient understands that death is a real possibility.

I find that people just want to know if there is hope. A different treatment regimen or a clinical trial may (or may not) extend their life. And while we cannot predict outcomes, we can give them hope. You can’t shut down hope. True for some people the cup is always half empty, but most people want to live and are optimistic no matter how small the chances are.

These conversations are very difficult. I don’t like them, but then I don’t avoid them either. Fortunately, patients don’t usually come to my office for the first visit presenting with advanced disease. In the cases I described above, one patient had been experiencing unexplained weight loss, but didn’t share it with a physician. And, for the patient with pancreatic cancer, other than some discomfort in the last couple of weeks, the disease was not associated with other symptoms. But the absence of symptoms should not in any way rule out a malignant disease. A diagnosis should be based on a complete evaluation of signs and symptoms followed by testing.

We’ve got to be able to take the time to listen to our patients during these encounters. We may not spend as much time as we should because we’re so busy now and we’re slaves to EMRs. It helps if we take more time to probe symptoms a little longer, especially in the primary care setting.

It is possible for a patient with cancer to be asymptomatic up until the later stages of the disease. A study published in ESMO Open in 2020 found that fewer than half of patients with stage 4 non–small cell lung cancer have only one or two symptoms at diagnosis regardless of whether the patient was a smoker. In this study only 33% of patients reported having a cough and 25% had chest pain.

A study presented in October at the United European Gastroenterology Week found that of 600 pancreatic cancer cases, 46 of these were not detected by CT or MRI conducted 3-18 months prior to diagnosis. Of the 46 cases, 26% were not picked up by the radiologist and the rest were largely as a result of imaging changes over time. Radiology techniques are good, but they cannot pick up lesions that are too small. And some lesions, particularly in pancreatic cancer, can grow and metastasize rather quickly.

When a patient is diagnosed with advanced disease, it is most often simply because of the nature of the disease. But sometimes patients put off scheduling a doctor visit because of fear of the potential for bad news or fear of the doctor belittling their symptoms. Some tell me they were “just hoping the symptoms would disappear.” Waiting too long to see a doctor is never a good idea because timing is crucial. In many cases, there is a small window of opportunity to treat disease if remission is to be achieved.


Dr. Henry is a practicing clinical oncologist with PennMedicine in Philadelphia where he also serves as Vice Chair of the Department of Medicine at Pennsylvania Hospital.
 

This article was updated 12/7/22.

It had only been 3 weeks since I first met this patient. She presented with an advanced case of colon cancer, but instead of treatment, we had to have a serious talk about death and dying and the goals of care. She died soon after our talk.

Within the course of 2 weeks I saw another new patient, but this time with pancreatic cancer that metastasized to the liver. “When can we start treatment?” he asked. Like my female patient with colon cancer, he was diagnosed too late as he was already in an incurable stage. He was shocked to learn that his condition was in stage 4, that achieving remission would be difficult and a cure, not likely. Certainly, standard of care treatments and clinical trials offered him hope, but they were unlikely to change the outcome.

We take a course in this – that is, in giving bad news, but every doctor has his or her own approach. Some are so uncomfortable with the talk, they choose avoidance and adopt the “look like you gotta go approach.” Or, the doctor may schedule another treatment or another test with the intention of avoiding end-of-life discussions. Other doctors opt for straight talk: “I think you should get your affairs in order. You’ve got 3 months to live.” These are extreme behaviors I wouldn’t recommend.

In my practice, I sit with my patients and explain the diagnosis. After discussing all options and the advanced stage and diagnosis, it ultimately comes down to “Win or lose, I will be here to take care of you.” Sometimes there is therapy that may help, but either way, the patient understands that death is a real possibility.

I find that people just want to know if there is hope. A different treatment regimen or a clinical trial may (or may not) extend their life. And while we cannot predict outcomes, we can give them hope. You can’t shut down hope. True for some people the cup is always half empty, but most people want to live and are optimistic no matter how small the chances are.

These conversations are very difficult. I don’t like them, but then I don’t avoid them either. Fortunately, patients don’t usually come to my office for the first visit presenting with advanced disease. In the cases I described above, one patient had been experiencing unexplained weight loss, but didn’t share it with a physician. And, for the patient with pancreatic cancer, other than some discomfort in the last couple of weeks, the disease was not associated with other symptoms. But the absence of symptoms should not in any way rule out a malignant disease. A diagnosis should be based on a complete evaluation of signs and symptoms followed by testing.

We’ve got to be able to take the time to listen to our patients during these encounters. We may not spend as much time as we should because we’re so busy now and we’re slaves to EMRs. It helps if we take more time to probe symptoms a little longer, especially in the primary care setting.

It is possible for a patient with cancer to be asymptomatic up until the later stages of the disease. A study published in ESMO Open in 2020 found that fewer than half of patients with stage 4 non–small cell lung cancer have only one or two symptoms at diagnosis regardless of whether the patient was a smoker. In this study only 33% of patients reported having a cough and 25% had chest pain.

A study presented in October at the United European Gastroenterology Week found that of 600 pancreatic cancer cases, 46 of these were not detected by CT or MRI conducted 3-18 months prior to diagnosis. Of the 46 cases, 26% were not picked up by the radiologist and the rest were largely as a result of imaging changes over time. Radiology techniques are good, but they cannot pick up lesions that are too small. And some lesions, particularly in pancreatic cancer, can grow and metastasize rather quickly.

When a patient is diagnosed with advanced disease, it is most often simply because of the nature of the disease. But sometimes patients put off scheduling a doctor visit because of fear of the potential for bad news or fear of the doctor belittling their symptoms. Some tell me they were “just hoping the symptoms would disappear.” Waiting too long to see a doctor is never a good idea because timing is crucial. In many cases, there is a small window of opportunity to treat disease if remission is to be achieved.


Dr. Henry is a practicing clinical oncologist with PennMedicine in Philadelphia where he also serves as Vice Chair of the Department of Medicine at Pennsylvania Hospital.
 

This article was updated 12/7/22.

Nearly two-thirds of patients with advanced non–small cell lung cancer (NSCLC) who are eligible for targeted therapy are not receiving these drugs because of gaps in clinical practice all along the cancer care spectrum, reveals a new analysis of data from U.S. practices.

For some of these patients, it could mean missing the chance for long-term survival or even cure.

One lung cancer patient, Janet Freeman-Daily, recently tweeted that she entered a targeted therapy clinical trial 10 years ago and is still taking the same, now approved, oral drug, with “no evidence of disease.”

Patients who have lung cancer with mutations that can be targeted with drug therapies – but who do not receive them – are missing this opportunity.

The new study suggests that there are many such patients. The researchers analyzed data on more than 38,000 patients with actively managed advanced NSCLC. They found that about half did not receive biomarker test results for a variety of reasons. But even among the half who were successfully tested, 30% of these patients did not receive the appropriate targeted therapies.

Overall, around 64% of eligible patients with advanced NSCLC are not benefiting from the most appropriate therapies, the team concludes.

The research was published online in JCO Precision Oncology.
 

Gaps in clinical practice

The high rate of failure points to clinical practice gaps in “many areas” across the cancer care spectrum, lead author Daryl Pritchard, PhD, from the Personalized Medicine Coalition, Washington, told this news organization.

“There’s various steps along the way that affect clinicians, laboratories, payers, the health providers [and] even patients,” he said. He added that product manufacturers also “have a role.”

“So it’s not an individual group that’s causing the problem. It’s a systemic awareness and systemic need to improve the delivery process.”

Dr. Pritchard underlined that the “the main goal of this analysis is to put everybody on alert that we need to do something about it.

“We need to – and this is easy to say but hard to do – evolve health care from a traditional one-size-fits-all mentality to a value-based strategy where you’re saying we want the best treatments” for patients, he said.

This means developing optimized and standardized laboratory processes, as well as clinical guidelines that set out the standard of care and optimized and integrated clinical decision support.

“We need to work as a community to demonstrate the value of this care and improve education and awareness to providers and payers,” Dr. Pritchard said. “That will encourage value-based practice coverage and reimbursement policies, and then also incentivize utilization in validated cases.”

Julie R. Brahmer, MD, who directs the thoracic oncology program at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, who was not involved with the study, said she was not sure whether she would say she was “surprised or disheartened” by the findings.

The study was focused on advanced NSCLC patients treated in 2019. Dr. Brahmer wondered whether the COVID-19 pandemic “might actually have made things worse.”

It will be important to “drill down” into some of the reasons why 30% of patients for whom biomarker testing results were available did not receive the appropriate treatment, she said.

Aside from cost-related problems, one factor at play could be whether the patient saw an oncologist, she said, while another could be that they went “straight to hospice” and were “not healthy enough to be able to tolerate” their targeted therapy.

Greater use of liquid biopsies, which identify biomarkers in the blood, are one way to improve access to biomarker testing, she suggested. It would help if these liquid biopsies were “consistently paid for by the payer, particularly for patients with advanced disease,” she added. Currently, payers often want patients to first undergo a tissue biopsy, which involves lung aspiration and may not be possible for some patients.

“If a Medicare patient is in the hospital when they have their biopsy or surgery, and then they have to wait 14 days in order for mutation tests to be ordered, and then if you add another 2 weeks for that test to come back, or even longer … [These delays] are some of the reasons why patients didn’t end up receiving therapy,” she elaborated.

“Some of these patients just can’t last that long before starting treatment,” she said.

Sandip P. Patel, MD, an oncologist at the Precision Immunotherapy Clinic at the University of California, San Diego, in La Jolla, wondered whether the issue is lack of education among physicians or whether there are potential financial problems. “Is there a financial risk to patients, for example, that is not being captured?” he mused.

It could also be a question of urban vs. rural centers, language barriers in communicating to patients, or other social determinants of health, he added.

At his institution (UCSD), there are “multiple choices” of molecular tests, each with “little nuances that differ among the tests that folks sometimes will take a look at in term of picking the best.

“But the best test is the one that gets done, and here we’re seeing no testing at all” for many patients, he said.

“It’s really unfortunate because for a lot of these patients, not only are they not getting the latest therapy, but they’re often getting something else that’s expensive and toxic instead,” Dr. Patel said.

Referring to the relatively high proportion of patients who didn’t receive targeted therapy even after being tested, he said, “For me, this study leaves more questions and answers.

“We’ve seen a lot of work in this space, showing us the problem,” Dr. Patel said. “What I haven’t yet seen is a very discrete analysis of the cause of that problem upstream.”
 

Cornerstone of personalized medicine

In their article, Dr. Pritchard and colleagues note that more than 90 targeted therapies have been approved by the U.S. Food and Drug Administration for use in eligible cancer patients. An estimated 55% of recent oncology trials involved the use of biomarkers.

Predictive biomarker testing to identify patients who may benefit from targeted therapies “is a cornerstone of personalized medicine in cancer care, allowing for more rapid diagnosis while informing treatment decisions that could lead to better patient outcomes and systemic efficiencies,” they emphasize.

However, providers “face several challenges” when integrating biomarker testing and targeted therapeutics into cancer care, and the use of biomarker testing varies widely across tumor types, biomarkers, and practice settings.

For their study, the team examined the use of targeted therapy in advanced NSCLC using data from the Diaceutics Data Repository, which includes commercial and Medicare claims, as well as laboratory data.

They focused on 38,068 patients with actively managed advanced NSCLC. Of those patients, 50.80% were women, and 64.6% were aged 71 years or older. The vast majority (84.50%) were non-Hispanic White patients.

The team examined the impact of seven clinical practice gaps on the timeline from ordering a biopsy to delivering targeted treatment. They then normalized the results to a standard patient population of 1,000.

In 6.6% of cases, an initial tissue or liquid biopsy was never performed, meaning that 66 of the 1,000 patients could not progress toward targeted therapy.

Among those who underwent a biopsy, for 4.0%, there was insufficient tissue on the initial biopsy, while for a further 0.97%, there was insufficient tissue on re-biopsy. Moreover, 9.6% could not undergo biopsy testing because of a lack of tumor tissue. Consequently, a further 136 of the 944 remaining patients were lost.

For the third clinical practice gap, the tumor cell content was overestimated in 1.7% of patients. As a result, their biopsy specimen could not be tested because it did not meet the threshold requirements. This resulted in the loss of a further 14 patients.

Moreover, for a further 17.5% of patients, biomarker testing was not ordered at all, owing to cost concerns, a lack of access to testing, a lack of awareness of testing options, and low confidence in the results, among other reasons. An additional 0.6% began treatment before any testing was ordered; together, that accounted for 142 patients being lost.

Even among patients who underwent biomarker testing, 14.5% had uninformative or inconclusive results, and 3.9% had false-negative results, meaning that a further 118 patients were lost.

In another 4.0% of cases, the results of biomarker testing did not arrive within the treatment decision window, owing to delays in reporting the results, and so for these patients, treatment began without the results being taken into consideration. A further 21 patients were lost.

The final clinical practice gap was not choosing the appropriate targeted treatment on the basis of test results. The researchers found that of 27,186 patients who underwent biomarker testing and received a timely result, 29.2% were not given the corresponding therapy. This resulted in the loss of a further 147 of the original 1,000 patients.

Overall, the team calculated that 64.4% of patients newly diagnosed with advanced NSCLC “are not benefiting from precision oncology care options appropriate for their diseases and will likely have suboptimal outcomes.”

The research was supported in part by the Personalized Medicine Coalition, a nonprofit 501c3 organization dedicated to the advancement of personalized medicine. Dr. Pritchard is an employee of the Personalized Medicine Coalition. A coauthor has relationships with Thermo Fisher Scientific, AstraZeneca, Eli Lilly, Blueprint Medicines, and Oncocyte.

A version of this article first appeared on Medscape.com.

Nearly two-thirds of patients with advanced non–small cell lung cancer (NSCLC) who are eligible for targeted therapy are not receiving these drugs because of gaps in clinical practice all along the cancer care spectrum, reveals a new analysis of data from U.S. practices.

For some of these patients, it could mean missing the chance for long-term survival or even cure.

One lung cancer patient, Janet Freeman-Daily, recently tweeted that she entered a targeted therapy clinical trial 10 years ago and is still taking the same, now approved, oral drug, with “no evidence of disease.”

Patients who have lung cancer with mutations that can be targeted with drug therapies – but who do not receive them – are missing this opportunity.

The new study suggests that there are many such patients. The researchers analyzed data on more than 38,000 patients with actively managed advanced NSCLC. They found that about half did not receive biomarker test results for a variety of reasons. But even among the half who were successfully tested, 30% of these patients did not receive the appropriate targeted therapies.

Overall, around 64% of eligible patients with advanced NSCLC are not benefiting from the most appropriate therapies, the team concludes.

The research was published online in JCO Precision Oncology.
 

Gaps in clinical practice

The high rate of failure points to clinical practice gaps in “many areas” across the cancer care spectrum, lead author Daryl Pritchard, PhD, from the Personalized Medicine Coalition, Washington, told this news organization.

“There’s various steps along the way that affect clinicians, laboratories, payers, the health providers [and] even patients,” he said. He added that product manufacturers also “have a role.”

“So it’s not an individual group that’s causing the problem. It’s a systemic awareness and systemic need to improve the delivery process.”

Dr. Pritchard underlined that the “the main goal of this analysis is to put everybody on alert that we need to do something about it.

“We need to – and this is easy to say but hard to do – evolve health care from a traditional one-size-fits-all mentality to a value-based strategy where you’re saying we want the best treatments” for patients, he said.

This means developing optimized and standardized laboratory processes, as well as clinical guidelines that set out the standard of care and optimized and integrated clinical decision support.

“We need to work as a community to demonstrate the value of this care and improve education and awareness to providers and payers,” Dr. Pritchard said. “That will encourage value-based practice coverage and reimbursement policies, and then also incentivize utilization in validated cases.”

Julie R. Brahmer, MD, who directs the thoracic oncology program at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, who was not involved with the study, said she was not sure whether she would say she was “surprised or disheartened” by the findings.

The study was focused on advanced NSCLC patients treated in 2019. Dr. Brahmer wondered whether the COVID-19 pandemic “might actually have made things worse.”

It will be important to “drill down” into some of the reasons why 30% of patients for whom biomarker testing results were available did not receive the appropriate treatment, she said.

Aside from cost-related problems, one factor at play could be whether the patient saw an oncologist, she said, while another could be that they went “straight to hospice” and were “not healthy enough to be able to tolerate” their targeted therapy.

Greater use of liquid biopsies, which identify biomarkers in the blood, are one way to improve access to biomarker testing, she suggested. It would help if these liquid biopsies were “consistently paid for by the payer, particularly for patients with advanced disease,” she added. Currently, payers often want patients to first undergo a tissue biopsy, which involves lung aspiration and may not be possible for some patients.

“If a Medicare patient is in the hospital when they have their biopsy or surgery, and then they have to wait 14 days in order for mutation tests to be ordered, and then if you add another 2 weeks for that test to come back, or even longer … [These delays] are some of the reasons why patients didn’t end up receiving therapy,” she elaborated.

“Some of these patients just can’t last that long before starting treatment,” she said.

Sandip P. Patel, MD, an oncologist at the Precision Immunotherapy Clinic at the University of California, San Diego, in La Jolla, wondered whether the issue is lack of education among physicians or whether there are potential financial problems. “Is there a financial risk to patients, for example, that is not being captured?” he mused.

It could also be a question of urban vs. rural centers, language barriers in communicating to patients, or other social determinants of health, he added.

At his institution (UCSD), there are “multiple choices” of molecular tests, each with “little nuances that differ among the tests that folks sometimes will take a look at in term of picking the best.

“But the best test is the one that gets done, and here we’re seeing no testing at all” for many patients, he said.

“It’s really unfortunate because for a lot of these patients, not only are they not getting the latest therapy, but they’re often getting something else that’s expensive and toxic instead,” Dr. Patel said.

Referring to the relatively high proportion of patients who didn’t receive targeted therapy even after being tested, he said, “For me, this study leaves more questions and answers.

“We’ve seen a lot of work in this space, showing us the problem,” Dr. Patel said. “What I haven’t yet seen is a very discrete analysis of the cause of that problem upstream.”
 

Cornerstone of personalized medicine

In their article, Dr. Pritchard and colleagues note that more than 90 targeted therapies have been approved by the U.S. Food and Drug Administration for use in eligible cancer patients. An estimated 55% of recent oncology trials involved the use of biomarkers.

Predictive biomarker testing to identify patients who may benefit from targeted therapies “is a cornerstone of personalized medicine in cancer care, allowing for more rapid diagnosis while informing treatment decisions that could lead to better patient outcomes and systemic efficiencies,” they emphasize.

However, providers “face several challenges” when integrating biomarker testing and targeted therapeutics into cancer care, and the use of biomarker testing varies widely across tumor types, biomarkers, and practice settings.

For their study, the team examined the use of targeted therapy in advanced NSCLC using data from the Diaceutics Data Repository, which includes commercial and Medicare claims, as well as laboratory data.

They focused on 38,068 patients with actively managed advanced NSCLC. Of those patients, 50.80% were women, and 64.6% were aged 71 years or older. The vast majority (84.50%) were non-Hispanic White patients.

The team examined the impact of seven clinical practice gaps on the timeline from ordering a biopsy to delivering targeted treatment. They then normalized the results to a standard patient population of 1,000.

In 6.6% of cases, an initial tissue or liquid biopsy was never performed, meaning that 66 of the 1,000 patients could not progress toward targeted therapy.

Among those who underwent a biopsy, for 4.0%, there was insufficient tissue on the initial biopsy, while for a further 0.97%, there was insufficient tissue on re-biopsy. Moreover, 9.6% could not undergo biopsy testing because of a lack of tumor tissue. Consequently, a further 136 of the 944 remaining patients were lost.

For the third clinical practice gap, the tumor cell content was overestimated in 1.7% of patients. As a result, their biopsy specimen could not be tested because it did not meet the threshold requirements. This resulted in the loss of a further 14 patients.

Moreover, for a further 17.5% of patients, biomarker testing was not ordered at all, owing to cost concerns, a lack of access to testing, a lack of awareness of testing options, and low confidence in the results, among other reasons. An additional 0.6% began treatment before any testing was ordered; together, that accounted for 142 patients being lost.

Even among patients who underwent biomarker testing, 14.5% had uninformative or inconclusive results, and 3.9% had false-negative results, meaning that a further 118 patients were lost.

In another 4.0% of cases, the results of biomarker testing did not arrive within the treatment decision window, owing to delays in reporting the results, and so for these patients, treatment began without the results being taken into consideration. A further 21 patients were lost.

The final clinical practice gap was not choosing the appropriate targeted treatment on the basis of test results. The researchers found that of 27,186 patients who underwent biomarker testing and received a timely result, 29.2% were not given the corresponding therapy. This resulted in the loss of a further 147 of the original 1,000 patients.

Overall, the team calculated that 64.4% of patients newly diagnosed with advanced NSCLC “are not benefiting from precision oncology care options appropriate for their diseases and will likely have suboptimal outcomes.”

The research was supported in part by the Personalized Medicine Coalition, a nonprofit 501c3 organization dedicated to the advancement of personalized medicine. Dr. Pritchard is an employee of the Personalized Medicine Coalition. A coauthor has relationships with Thermo Fisher Scientific, AstraZeneca, Eli Lilly, Blueprint Medicines, and Oncocyte.

A version of this article first appeared on Medscape.com.

Nearly two-thirds of patients with advanced non–small cell lung cancer (NSCLC) who are eligible for targeted therapy are not receiving these drugs because of gaps in clinical practice all along the cancer care spectrum, reveals a new analysis of data from U.S. practices.

For some of these patients, it could mean missing the chance for long-term survival or even cure.

One lung cancer patient, Janet Freeman-Daily, recently tweeted that she entered a targeted therapy clinical trial 10 years ago and is still taking the same, now approved, oral drug, with “no evidence of disease.”

Patients who have lung cancer with mutations that can be targeted with drug therapies – but who do not receive them – are missing this opportunity.

The new study suggests that there are many such patients. The researchers analyzed data on more than 38,000 patients with actively managed advanced NSCLC. They found that about half did not receive biomarker test results for a variety of reasons. But even among the half who were successfully tested, 30% of these patients did not receive the appropriate targeted therapies.

Overall, around 64% of eligible patients with advanced NSCLC are not benefiting from the most appropriate therapies, the team concludes.

The research was published online in JCO Precision Oncology.
 

Gaps in clinical practice

The high rate of failure points to clinical practice gaps in “many areas” across the cancer care spectrum, lead author Daryl Pritchard, PhD, from the Personalized Medicine Coalition, Washington, told this news organization.

“There’s various steps along the way that affect clinicians, laboratories, payers, the health providers [and] even patients,” he said. He added that product manufacturers also “have a role.”

“So it’s not an individual group that’s causing the problem. It’s a systemic awareness and systemic need to improve the delivery process.”

Dr. Pritchard underlined that the “the main goal of this analysis is to put everybody on alert that we need to do something about it.

“We need to – and this is easy to say but hard to do – evolve health care from a traditional one-size-fits-all mentality to a value-based strategy where you’re saying we want the best treatments” for patients, he said.

This means developing optimized and standardized laboratory processes, as well as clinical guidelines that set out the standard of care and optimized and integrated clinical decision support.

“We need to work as a community to demonstrate the value of this care and improve education and awareness to providers and payers,” Dr. Pritchard said. “That will encourage value-based practice coverage and reimbursement policies, and then also incentivize utilization in validated cases.”

Julie R. Brahmer, MD, who directs the thoracic oncology program at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, who was not involved with the study, said she was not sure whether she would say she was “surprised or disheartened” by the findings.

The study was focused on advanced NSCLC patients treated in 2019. Dr. Brahmer wondered whether the COVID-19 pandemic “might actually have made things worse.”

It will be important to “drill down” into some of the reasons why 30% of patients for whom biomarker testing results were available did not receive the appropriate treatment, she said.

Aside from cost-related problems, one factor at play could be whether the patient saw an oncologist, she said, while another could be that they went “straight to hospice” and were “not healthy enough to be able to tolerate” their targeted therapy.

Greater use of liquid biopsies, which identify biomarkers in the blood, are one way to improve access to biomarker testing, she suggested. It would help if these liquid biopsies were “consistently paid for by the payer, particularly for patients with advanced disease,” she added. Currently, payers often want patients to first undergo a tissue biopsy, which involves lung aspiration and may not be possible for some patients.

“If a Medicare patient is in the hospital when they have their biopsy or surgery, and then they have to wait 14 days in order for mutation tests to be ordered, and then if you add another 2 weeks for that test to come back, or even longer … [These delays] are some of the reasons why patients didn’t end up receiving therapy,” she elaborated.

“Some of these patients just can’t last that long before starting treatment,” she said.

Sandip P. Patel, MD, an oncologist at the Precision Immunotherapy Clinic at the University of California, San Diego, in La Jolla, wondered whether the issue is lack of education among physicians or whether there are potential financial problems. “Is there a financial risk to patients, for example, that is not being captured?” he mused.

It could also be a question of urban vs. rural centers, language barriers in communicating to patients, or other social determinants of health, he added.

At his institution (UCSD), there are “multiple choices” of molecular tests, each with “little nuances that differ among the tests that folks sometimes will take a look at in term of picking the best.

“But the best test is the one that gets done, and here we’re seeing no testing at all” for many patients, he said.

“It’s really unfortunate because for a lot of these patients, not only are they not getting the latest therapy, but they’re often getting something else that’s expensive and toxic instead,” Dr. Patel said.

Referring to the relatively high proportion of patients who didn’t receive targeted therapy even after being tested, he said, “For me, this study leaves more questions and answers.

“We’ve seen a lot of work in this space, showing us the problem,” Dr. Patel said. “What I haven’t yet seen is a very discrete analysis of the cause of that problem upstream.”
 

Cornerstone of personalized medicine

In their article, Dr. Pritchard and colleagues note that more than 90 targeted therapies have been approved by the U.S. Food and Drug Administration for use in eligible cancer patients. An estimated 55% of recent oncology trials involved the use of biomarkers.

Predictive biomarker testing to identify patients who may benefit from targeted therapies “is a cornerstone of personalized medicine in cancer care, allowing for more rapid diagnosis while informing treatment decisions that could lead to better patient outcomes and systemic efficiencies,” they emphasize.

However, providers “face several challenges” when integrating biomarker testing and targeted therapeutics into cancer care, and the use of biomarker testing varies widely across tumor types, biomarkers, and practice settings.

For their study, the team examined the use of targeted therapy in advanced NSCLC using data from the Diaceutics Data Repository, which includes commercial and Medicare claims, as well as laboratory data.

They focused on 38,068 patients with actively managed advanced NSCLC. Of those patients, 50.80% were women, and 64.6% were aged 71 years or older. The vast majority (84.50%) were non-Hispanic White patients.

The team examined the impact of seven clinical practice gaps on the timeline from ordering a biopsy to delivering targeted treatment. They then normalized the results to a standard patient population of 1,000.

In 6.6% of cases, an initial tissue or liquid biopsy was never performed, meaning that 66 of the 1,000 patients could not progress toward targeted therapy.

Among those who underwent a biopsy, for 4.0%, there was insufficient tissue on the initial biopsy, while for a further 0.97%, there was insufficient tissue on re-biopsy. Moreover, 9.6% could not undergo biopsy testing because of a lack of tumor tissue. Consequently, a further 136 of the 944 remaining patients were lost.

For the third clinical practice gap, the tumor cell content was overestimated in 1.7% of patients. As a result, their biopsy specimen could not be tested because it did not meet the threshold requirements. This resulted in the loss of a further 14 patients.

Moreover, for a further 17.5% of patients, biomarker testing was not ordered at all, owing to cost concerns, a lack of access to testing, a lack of awareness of testing options, and low confidence in the results, among other reasons. An additional 0.6% began treatment before any testing was ordered; together, that accounted for 142 patients being lost.

Even among patients who underwent biomarker testing, 14.5% had uninformative or inconclusive results, and 3.9% had false-negative results, meaning that a further 118 patients were lost.

In another 4.0% of cases, the results of biomarker testing did not arrive within the treatment decision window, owing to delays in reporting the results, and so for these patients, treatment began without the results being taken into consideration. A further 21 patients were lost.

The final clinical practice gap was not choosing the appropriate targeted treatment on the basis of test results. The researchers found that of 27,186 patients who underwent biomarker testing and received a timely result, 29.2% were not given the corresponding therapy. This resulted in the loss of a further 147 of the original 1,000 patients.

Overall, the team calculated that 64.4% of patients newly diagnosed with advanced NSCLC “are not benefiting from precision oncology care options appropriate for their diseases and will likely have suboptimal outcomes.”

The research was supported in part by the Personalized Medicine Coalition, a nonprofit 501c3 organization dedicated to the advancement of personalized medicine. Dr. Pritchard is an employee of the Personalized Medicine Coalition. A coauthor has relationships with Thermo Fisher Scientific, AstraZeneca, Eli Lilly, Blueprint Medicines, and Oncocyte.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has announced it will not approve the investigational drug poziotinib (Spectrum Pharmaceuticals) for the treatment of certain patients with non–small cell lung cancer (NSCLC).

The clinical data the company submitted were deemed insufficient for approval, and additional data including a randomized clinical trial would be needed, the agency said.

The move is not a surprise, as the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-4 against approval when it met to discuss the drug in September, as reported at the time by this news organization.

Poziotinib was developed for patients with previously treated locally advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations, which occur in about 2% of patients with NSCLC.

Poziotinib is a potent oral pan-HER tyrosine kinase inhibitor with activity in patients with these mutations. Clinical data from the ZENITH20 Trial reported last year showed an overall response rate of 43.8%, and the drug was described as showing “clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.”

“We continue to believe that poziotinib could present a meaningful treatment option for patients with this rare form of lung cancer, for whom other therapies have failed,” commented Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals. 

However, following multiple interactions with the FDA, “we have made the strategic decision to immediately deprioritize the poziotinib program,” he said. The change is effective immediately, and the company is now in the process of reducing its R&D workforce by approximately 75%.
 

Drug development criticized

At the ODAC meeting, several panelists were openly critical of the approach Spectrum took in developing the drug. The FDA’s top cancer official, Richard Pazdur, MD, characterized Spectrum’s work as “poor drug development” and likened it to “building a house on quicksand.”

The FDA panel detailed several ways they felt that the poziotinib application fell short of the benchmarks needed for accelerated approval.

To win such a speedy clearance, a company needs to show that a drug provides a meaningful therapeutic benefit over existing treatments. The panel argued that, so far, poziotinib appears to be inferior to a product already available for HER2-mutant NSCLC, trastuzumab deruxtecan (Enhertu), which received accelerated approval in August.

The FDA staff contrasted a reported overall response rate for poziotinib, which was estimated at 28% (from data discussed at the meeting), with the overall response rate for trastuzumab deruxtecan, which is 58%.

Harpreet Singh, MD, a director in the FDA’s oncology division, asked the panel to consider what they would do as a physician treating a patient with this mutation, given the choices that are now available.

“That’s something we’re asking the committee to consider … to think about the context of what’s available to you in the clinic,” Dr. Singh said.

Dr. Singh said she expected that patients and physicians would prefer a drug such as trastuzumab deruxtecan, which has a more established record, regardless of the fact that treatment with poziotinib is more convenient because it is given as a tablet.

Dr. Singh and other staff also raised concerns about side effects of poziotinib, including diarrhea, as well as difficulty determining the right dose.

Katherine Scilla, MD, one of the nine ODAC panelists to vote “no,” echoed these views. Although Dr. Scilla, an oncologist at the University of Maryland, Baltimore, sympathized with the need for options for people with this rare form of lung cancer, she was not persuaded by the data on poziotinib that were presented to support accelerated approval.

“I’m not sure that this represents a meaningful therapeutic benefit over other agents,” she said at the time. 

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has announced it will not approve the investigational drug poziotinib (Spectrum Pharmaceuticals) for the treatment of certain patients with non–small cell lung cancer (NSCLC).

The clinical data the company submitted were deemed insufficient for approval, and additional data including a randomized clinical trial would be needed, the agency said.

The move is not a surprise, as the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-4 against approval when it met to discuss the drug in September, as reported at the time by this news organization.

Poziotinib was developed for patients with previously treated locally advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations, which occur in about 2% of patients with NSCLC.

Poziotinib is a potent oral pan-HER tyrosine kinase inhibitor with activity in patients with these mutations. Clinical data from the ZENITH20 Trial reported last year showed an overall response rate of 43.8%, and the drug was described as showing “clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.”

“We continue to believe that poziotinib could present a meaningful treatment option for patients with this rare form of lung cancer, for whom other therapies have failed,” commented Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals. 

However, following multiple interactions with the FDA, “we have made the strategic decision to immediately deprioritize the poziotinib program,” he said. The change is effective immediately, and the company is now in the process of reducing its R&D workforce by approximately 75%.
 

Drug development criticized

At the ODAC meeting, several panelists were openly critical of the approach Spectrum took in developing the drug. The FDA’s top cancer official, Richard Pazdur, MD, characterized Spectrum’s work as “poor drug development” and likened it to “building a house on quicksand.”

The FDA panel detailed several ways they felt that the poziotinib application fell short of the benchmarks needed for accelerated approval.

To win such a speedy clearance, a company needs to show that a drug provides a meaningful therapeutic benefit over existing treatments. The panel argued that, so far, poziotinib appears to be inferior to a product already available for HER2-mutant NSCLC, trastuzumab deruxtecan (Enhertu), which received accelerated approval in August.

The FDA staff contrasted a reported overall response rate for poziotinib, which was estimated at 28% (from data discussed at the meeting), with the overall response rate for trastuzumab deruxtecan, which is 58%.

Harpreet Singh, MD, a director in the FDA’s oncology division, asked the panel to consider what they would do as a physician treating a patient with this mutation, given the choices that are now available.

“That’s something we’re asking the committee to consider … to think about the context of what’s available to you in the clinic,” Dr. Singh said.

Dr. Singh said she expected that patients and physicians would prefer a drug such as trastuzumab deruxtecan, which has a more established record, regardless of the fact that treatment with poziotinib is more convenient because it is given as a tablet.

Dr. Singh and other staff also raised concerns about side effects of poziotinib, including diarrhea, as well as difficulty determining the right dose.

Katherine Scilla, MD, one of the nine ODAC panelists to vote “no,” echoed these views. Although Dr. Scilla, an oncologist at the University of Maryland, Baltimore, sympathized with the need for options for people with this rare form of lung cancer, she was not persuaded by the data on poziotinib that were presented to support accelerated approval.

“I’m not sure that this represents a meaningful therapeutic benefit over other agents,” she said at the time. 

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has announced it will not approve the investigational drug poziotinib (Spectrum Pharmaceuticals) for the treatment of certain patients with non–small cell lung cancer (NSCLC).

The clinical data the company submitted were deemed insufficient for approval, and additional data including a randomized clinical trial would be needed, the agency said.

The move is not a surprise, as the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-4 against approval when it met to discuss the drug in September, as reported at the time by this news organization.

Poziotinib was developed for patients with previously treated locally advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations, which occur in about 2% of patients with NSCLC.

Poziotinib is a potent oral pan-HER tyrosine kinase inhibitor with activity in patients with these mutations. Clinical data from the ZENITH20 Trial reported last year showed an overall response rate of 43.8%, and the drug was described as showing “clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.”

“We continue to believe that poziotinib could present a meaningful treatment option for patients with this rare form of lung cancer, for whom other therapies have failed,” commented Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals. 

However, following multiple interactions with the FDA, “we have made the strategic decision to immediately deprioritize the poziotinib program,” he said. The change is effective immediately, and the company is now in the process of reducing its R&D workforce by approximately 75%.
 

Drug development criticized

At the ODAC meeting, several panelists were openly critical of the approach Spectrum took in developing the drug. The FDA’s top cancer official, Richard Pazdur, MD, characterized Spectrum’s work as “poor drug development” and likened it to “building a house on quicksand.”

The FDA panel detailed several ways they felt that the poziotinib application fell short of the benchmarks needed for accelerated approval.

To win such a speedy clearance, a company needs to show that a drug provides a meaningful therapeutic benefit over existing treatments. The panel argued that, so far, poziotinib appears to be inferior to a product already available for HER2-mutant NSCLC, trastuzumab deruxtecan (Enhertu), which received accelerated approval in August.

The FDA staff contrasted a reported overall response rate for poziotinib, which was estimated at 28% (from data discussed at the meeting), with the overall response rate for trastuzumab deruxtecan, which is 58%.

Harpreet Singh, MD, a director in the FDA’s oncology division, asked the panel to consider what they would do as a physician treating a patient with this mutation, given the choices that are now available.

“That’s something we’re asking the committee to consider … to think about the context of what’s available to you in the clinic,” Dr. Singh said.

Dr. Singh said she expected that patients and physicians would prefer a drug such as trastuzumab deruxtecan, which has a more established record, regardless of the fact that treatment with poziotinib is more convenient because it is given as a tablet.

Dr. Singh and other staff also raised concerns about side effects of poziotinib, including diarrhea, as well as difficulty determining the right dose.

Katherine Scilla, MD, one of the nine ODAC panelists to vote “no,” echoed these views. Although Dr. Scilla, an oncologist at the University of Maryland, Baltimore, sympathized with the need for options for people with this rare form of lung cancer, she was not persuaded by the data on poziotinib that were presented to support accelerated approval.

“I’m not sure that this represents a meaningful therapeutic benefit over other agents,” she said at the time. 

A version of this article first appeared on Medscape.com.

CHICAGO – Discovering lung cancer early with annual low-dose computed tomography greatly improves long-term survival rates to 80%, findings from a 20-year international study indicate.

Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.

The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.

Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
 

Participants’ 20-year survival rate 80%

Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.

Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.

For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).

No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.

These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.

At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.

Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.

When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.

“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.

“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
 

Findings “very promising”

Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.

“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.

“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.

Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.

So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.

“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.

Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.

Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHICAGO – Discovering lung cancer early with annual low-dose computed tomography greatly improves long-term survival rates to 80%, findings from a 20-year international study indicate.

Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.

The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.

Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
 

Participants’ 20-year survival rate 80%

Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.

Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.

For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).

No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.

These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.

At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.

Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.

When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.

“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.

“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
 

Findings “very promising”

Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.

“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.

“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.

Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.

So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.

“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.

Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.

Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHICAGO – Discovering lung cancer early with annual low-dose computed tomography greatly improves long-term survival rates to 80%, findings from a 20-year international study indicate.

Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.

The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.

Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
 

Participants’ 20-year survival rate 80%

Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.

Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.

For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).

No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.

These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.

At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.

Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.

When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.

“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.

“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
 

Findings “very promising”

Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.

“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.

“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.

Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.

So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.

“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.

Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.

Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a phase 2 clinical trial of the soluble lymphocyte-activation gene 3 (LAG-3) as a potential treatment for non–small cell lung cancer (NSCLC), the drug performed well across all levels of PD-L1 expression.

“We observed a very encouraging response rate. Responses were seen across PD-L1 status,” said Wade Iams, MD, at a press conference held in advance of the annual meeting of the Society for Immunotherapy of Cancer. Dr. Iams is a professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn.

“The study was not loaded to PD-L1–high patients. We had a good breakdown across all of our three typical groups in the [NSCLC] treatment setting. Across histology types between squamous and nonsquamous, the median duration of response was almost 22 months. This is very encouraging compared to historical controls,” he said.

Eftilagimod alpha is a soluble form of the LAG-3 protein, which is a stimulator of antigen-presenting cells and CD8+ T cells through its action on MHC class 2 molecules. It suppresses the activation of T cells and therefore has the potential to boost the effect of anti–PD-1 therapy. LAG-3 can have both stimulatory and inhibitor immune effects, leading Immutep, which sponsored the study with Merck Sharp and Dohme, to pursue it in both cancer immunotherapy and autoimmune diseases.

The drug is a departure from other drugs which are LAG-3 antagonists. Those therapies interfere with the interaction between LAG-3 on the surface of activated T cells and MHC class 2 molecules on the surface of resting dendritic cells, which would otherwise dampen immune response in the tumor microenvironment. On the other hand, LAG-3 (or eftilagimod alpha) interacts with MHC class 2 on the surface of activated dendritic cells and monocytes to stimulate production of cytotoxic CD8+ T cells. These in turn can be unleashed further by the downstream action of pembrolizumab.

The phase 2 trial included three parts: In part A, 114 patients with NSCLC received the combination of eftilagimod alpha and pembrolizumab being given as a first-line therapy. Part B looked at the combination in 36 patents who were resistant to PD-1/PD-L1 therapies. Part C included 39 patients with head and neck squamous cell carcinoma who had previously received platinum-based chemotherapy. Patients received combination therapy for up to 1 year, then monotherapy with pembrolizumab for up to another year.

The primary endpoint of the study was a comparison of overall response rate to historical controls, with success set at 35% or higher. In the intent-to-treat analysis of the treatment-naive NSCLC population, ORR was 39.5% (95% confidence interval, 30.5%-49.1%) and the interim median progression-free survival was 6.9 months (95% CI, 4.9-9.3 months). Among 40 responders, the median duration of response was 21.6 months (95% CI, 17.3-30.0 months). ORRs were similar between squamous and nonsquamous subtypes.

In his presentation of the results, Dr. Iams said that 75% of participants had PD-L1 levels below 50%. The ORR was highest at 55% in the PD-L1 greater than 50% group, 44.7% in the PD-L1 1%-49% group, and 31.1% in the PD-L1 less than 1% group. It was a “very impressive response rate” for the low PD-L1 group, Dr. Iams said. Interim median progression-free survival followed a similar trend, with values of 11.4 months, 8.3 months, and 4.2 months, respectively.

Asked about the efficacy across subgroups, Dr. Iams responded that other immune stimulating agents have shown a stepwise improvement across PD-L1 expression levels, similar to what was observed in the current study. “My personal opinion as to why it was still effective at low PD-L1 is in part that PD-L1 is an imperfect biomarker. We know that there’s tumor heterogeneity, and perhaps it’s not fully representative of a one-site evaluation, but also in combination, and we have seen this in patients with [NSCLC] treated with both PD-L1 and CTLA-4 agents of increased efficacy in the PD-L1–low patients. So these combination immunotherapy strategies may be uniquely opportune for the low PD-L1 patients,” Dr. Iams said.

The study was funded by Immutep and Merck Sharp and Dohme. Dr. Iams has financial relationships with Merck.

In a phase 2 clinical trial of the soluble lymphocyte-activation gene 3 (LAG-3) as a potential treatment for non–small cell lung cancer (NSCLC), the drug performed well across all levels of PD-L1 expression.

“We observed a very encouraging response rate. Responses were seen across PD-L1 status,” said Wade Iams, MD, at a press conference held in advance of the annual meeting of the Society for Immunotherapy of Cancer. Dr. Iams is a professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn.

“The study was not loaded to PD-L1–high patients. We had a good breakdown across all of our three typical groups in the [NSCLC] treatment setting. Across histology types between squamous and nonsquamous, the median duration of response was almost 22 months. This is very encouraging compared to historical controls,” he said.

Eftilagimod alpha is a soluble form of the LAG-3 protein, which is a stimulator of antigen-presenting cells and CD8+ T cells through its action on MHC class 2 molecules. It suppresses the activation of T cells and therefore has the potential to boost the effect of anti–PD-1 therapy. LAG-3 can have both stimulatory and inhibitor immune effects, leading Immutep, which sponsored the study with Merck Sharp and Dohme, to pursue it in both cancer immunotherapy and autoimmune diseases.

The drug is a departure from other drugs which are LAG-3 antagonists. Those therapies interfere with the interaction between LAG-3 on the surface of activated T cells and MHC class 2 molecules on the surface of resting dendritic cells, which would otherwise dampen immune response in the tumor microenvironment. On the other hand, LAG-3 (or eftilagimod alpha) interacts with MHC class 2 on the surface of activated dendritic cells and monocytes to stimulate production of cytotoxic CD8+ T cells. These in turn can be unleashed further by the downstream action of pembrolizumab.

The phase 2 trial included three parts: In part A, 114 patients with NSCLC received the combination of eftilagimod alpha and pembrolizumab being given as a first-line therapy. Part B looked at the combination in 36 patents who were resistant to PD-1/PD-L1 therapies. Part C included 39 patients with head and neck squamous cell carcinoma who had previously received platinum-based chemotherapy. Patients received combination therapy for up to 1 year, then monotherapy with pembrolizumab for up to another year.

The primary endpoint of the study was a comparison of overall response rate to historical controls, with success set at 35% or higher. In the intent-to-treat analysis of the treatment-naive NSCLC population, ORR was 39.5% (95% confidence interval, 30.5%-49.1%) and the interim median progression-free survival was 6.9 months (95% CI, 4.9-9.3 months). Among 40 responders, the median duration of response was 21.6 months (95% CI, 17.3-30.0 months). ORRs were similar between squamous and nonsquamous subtypes.

In his presentation of the results, Dr. Iams said that 75% of participants had PD-L1 levels below 50%. The ORR was highest at 55% in the PD-L1 greater than 50% group, 44.7% in the PD-L1 1%-49% group, and 31.1% in the PD-L1 less than 1% group. It was a “very impressive response rate” for the low PD-L1 group, Dr. Iams said. Interim median progression-free survival followed a similar trend, with values of 11.4 months, 8.3 months, and 4.2 months, respectively.

Asked about the efficacy across subgroups, Dr. Iams responded that other immune stimulating agents have shown a stepwise improvement across PD-L1 expression levels, similar to what was observed in the current study. “My personal opinion as to why it was still effective at low PD-L1 is in part that PD-L1 is an imperfect biomarker. We know that there’s tumor heterogeneity, and perhaps it’s not fully representative of a one-site evaluation, but also in combination, and we have seen this in patients with [NSCLC] treated with both PD-L1 and CTLA-4 agents of increased efficacy in the PD-L1–low patients. So these combination immunotherapy strategies may be uniquely opportune for the low PD-L1 patients,” Dr. Iams said.

The study was funded by Immutep and Merck Sharp and Dohme. Dr. Iams has financial relationships with Merck.

In a phase 2 clinical trial of the soluble lymphocyte-activation gene 3 (LAG-3) as a potential treatment for non–small cell lung cancer (NSCLC), the drug performed well across all levels of PD-L1 expression.

“We observed a very encouraging response rate. Responses were seen across PD-L1 status,” said Wade Iams, MD, at a press conference held in advance of the annual meeting of the Society for Immunotherapy of Cancer. Dr. Iams is a professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn.

“The study was not loaded to PD-L1–high patients. We had a good breakdown across all of our three typical groups in the [NSCLC] treatment setting. Across histology types between squamous and nonsquamous, the median duration of response was almost 22 months. This is very encouraging compared to historical controls,” he said.

Eftilagimod alpha is a soluble form of the LAG-3 protein, which is a stimulator of antigen-presenting cells and CD8+ T cells through its action on MHC class 2 molecules. It suppresses the activation of T cells and therefore has the potential to boost the effect of anti–PD-1 therapy. LAG-3 can have both stimulatory and inhibitor immune effects, leading Immutep, which sponsored the study with Merck Sharp and Dohme, to pursue it in both cancer immunotherapy and autoimmune diseases.

The drug is a departure from other drugs which are LAG-3 antagonists. Those therapies interfere with the interaction between LAG-3 on the surface of activated T cells and MHC class 2 molecules on the surface of resting dendritic cells, which would otherwise dampen immune response in the tumor microenvironment. On the other hand, LAG-3 (or eftilagimod alpha) interacts with MHC class 2 on the surface of activated dendritic cells and monocytes to stimulate production of cytotoxic CD8+ T cells. These in turn can be unleashed further by the downstream action of pembrolizumab.

The phase 2 trial included three parts: In part A, 114 patients with NSCLC received the combination of eftilagimod alpha and pembrolizumab being given as a first-line therapy. Part B looked at the combination in 36 patents who were resistant to PD-1/PD-L1 therapies. Part C included 39 patients with head and neck squamous cell carcinoma who had previously received platinum-based chemotherapy. Patients received combination therapy for up to 1 year, then monotherapy with pembrolizumab for up to another year.

The primary endpoint of the study was a comparison of overall response rate to historical controls, with success set at 35% or higher. In the intent-to-treat analysis of the treatment-naive NSCLC population, ORR was 39.5% (95% confidence interval, 30.5%-49.1%) and the interim median progression-free survival was 6.9 months (95% CI, 4.9-9.3 months). Among 40 responders, the median duration of response was 21.6 months (95% CI, 17.3-30.0 months). ORRs were similar between squamous and nonsquamous subtypes.

In his presentation of the results, Dr. Iams said that 75% of participants had PD-L1 levels below 50%. The ORR was highest at 55% in the PD-L1 greater than 50% group, 44.7% in the PD-L1 1%-49% group, and 31.1% in the PD-L1 less than 1% group. It was a “very impressive response rate” for the low PD-L1 group, Dr. Iams said. Interim median progression-free survival followed a similar trend, with values of 11.4 months, 8.3 months, and 4.2 months, respectively.

Asked about the efficacy across subgroups, Dr. Iams responded that other immune stimulating agents have shown a stepwise improvement across PD-L1 expression levels, similar to what was observed in the current study. “My personal opinion as to why it was still effective at low PD-L1 is in part that PD-L1 is an imperfect biomarker. We know that there’s tumor heterogeneity, and perhaps it’s not fully representative of a one-site evaluation, but also in combination, and we have seen this in patients with [NSCLC] treated with both PD-L1 and CTLA-4 agents of increased efficacy in the PD-L1–low patients. So these combination immunotherapy strategies may be uniquely opportune for the low PD-L1 patients,” Dr. Iams said.

The study was funded by Immutep and Merck Sharp and Dohme. Dr. Iams has financial relationships with Merck.

It’s a “champagne problem” many of us have encountered over the past few years in the clinic.

A patient with advanced non–small cell lung cancer (NSCLC) is fortunate enough to continue to do well for 2 years on ongoing pembrolizumab or perhaps pemetrexed and pembrolizumab as maintenance therapy. The latest CT shows a residual but far smaller primary tumor than what she started with.

In this instance, you may be considering stopping treatment but are concerned about doing so with evidence of disease still present.

Clinical trials of immunotherapy or chemoimmunotherapy have generally terminated treatment in nonprogressing patients after 2 years. We also know that some patients in early trials of immunotherapy stopped treatment after a fixed period of 1 or 2 years and continued to show no evidence of progression many years later.

The reason some patients experience this kind of success: Unlike the mechanism of action of conventional chemotherapy or targeted therapies, where ongoing treatment would be important to continue to exert an inhibitory effect, the active substrate of immunotherapy is the patient’s immune system, which can potentially have a self-sustaining efficacy beyond the stimulatory effect of the checkpoint inhibitor.

Though we don’t want to overtreat our patients, the question remains: Will patients do just as well off treatment, with the potential to resume as needed?

One trial directly addressed this question of stopping vs. continuing treatment in patients on immunotherapy. The CheckMate 153 trial, published in 2020, randomly assigned 252 previously treated patients who hadn’t demonstrated progression after 1 year on nivolumab to either discontinue nivolumab or continue nivolumab on an ongoing basis. The results were strongly in favor of ongoing therapy. Both progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who continued therapy: PFS of 24.7 months vs. 9.4 months and OS not reached vs. 32.5 months.

This finding is important, but there’s an important caveat. The study population included many heavily pretreated patients, but, in practice, immunotherapy has generally moved into the first-line setting, where we see dramatic responses in a significant subset of patients.

Even more recent data are emerging that may help us evaluate who will do well off therapy and who should continue treatment.

We now have a growing collection of long-term data on patients who are more likely to have good outcomes with immunotherapy, specifically those with high tumor programmed death-ligand 1 (PD-L1) expression (≥ 50%), from the KEYNOTE-024 trial. In this study, 39 of 151 (25.8%) patients assigned to pembrolizumab completed the planned maximum of 2 years of treatment, among whom 82.1% achieved an objective response; but, only 10% (4 patients) achieved a complete response. The proportion of patients without progression and remaining off therapy wasn’t reported, but the OS rate 3 years after completing treatment was 81.4%.

In addition, restarting immunotherapy after discontinuing appears to be a moderately effective strategy. In the KEYNOTE-024 trial, 12 patients received a second course of pembrolizumab because of disease progression a median of 15.2 months after discontinuing pembrolizumab. In this small cohort, eight of these patients (66.7%) were alive at the data cutoff, and six (50%) achieved stable disease.

Recently, we received additional insight in the follow-up from two chemoimmunotherapy trials that have most shaped my practice for patients with advanced NSCLC and any level of PD-L1 expression. These are the KEYNOTE-189 trial of platinum-pemetrexed with pembrolizumab vs. placebo in those with nonsquamous NSCLC, and the KEYNOTE-407 trial of carboplatin-taxane with pembrolizumab vs. placebo in patients with advanced squamous NSCLC. The National Comprehensive Cancer Network has designated each as a “preferred regimen” for patients with advanced NSCLC.

Both regimens have demonstrated sustained efficacy benefits with prolonged follow-up, including significantly superior objective response rate, PFS, and OS with the addition of pembrolizumab. These findings merely cemented the role of these regimens in our practice, but the trials also reported on the cohort of patients who completed 35 cycles of treatment over 2 years then discontinued therapy. In both, the majority of patients showed an objective response (86% in KEYNOTE-189 and 90% in KEYNOTE-407), with most patients alive at 3 years after 2 years of treatment (71.9% in KEYNOTE-189 and 69.5% in KEYNOTE-407). In addition, the proportion of patients alive without disease progression or subsequent therapy was notable – 40.4% in KEYNOTE-189 and 43.6% KEYNOTE-407.

How should we interpret these data for the patient who is in the exam room with us?

The short answer is that we don’t know. I see this as a half-empty, half-full conundrum.

I’m disappointed that more patients who responded for 2 years will experience disease progression in the 1-3 years that follow. This signals that their immune systems have not perpetuated their initial response over the long-term. But these patients may have demonstrated disease progression even if they had continued therapy.

We also know that some patients can be rechallenged and will respond again. Some of these patients will show stable disease, whereas others will progress with repeat treatment. I would love to be able to better predict which patients are destined to do well without treatment vs. those who benefit from treatment beyond 2 years.

Might the level of PD-L1 expression tell us? Can PET imaging discriminate those with residual hypermetabolism who may need continued treatment from those with no residual uptake who could be spared it? Would serial measurement of circulating tumor DNA (ctDNA) in responding patients identify when they have achieved a point of diminishing returns, potentially indicating that some can safely discontinue treatment after 2 years, whereas others need to continue to suppress on prolonged maintenance therapy?

These questions have yet to be studied systematically. In the meantime, I take an individualized approach with my patients facing this decision. Some have experienced escalating arthralgias and myalgias, cost concerns, or other issues related to immunotherapy that may dissuade us from continuing treatment. But several others have been grateful to continue with their treatment, hesitant to do anything that could change the path of their disease.

In my patients who tolerate therapy well, I’m more worried about potential undertreatment than overtreatment. I tend to favor having my patients continue therapy in the absence of problematic toxicity or practical challenges. There is certainly room for debate here while we await data to better guide these decisions. How do you approach these patients?

Dr. West is Clinical Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

A version of this article first appeared on Medscape.com.

It’s a “champagne problem” many of us have encountered over the past few years in the clinic.

A patient with advanced non–small cell lung cancer (NSCLC) is fortunate enough to continue to do well for 2 years on ongoing pembrolizumab or perhaps pemetrexed and pembrolizumab as maintenance therapy. The latest CT shows a residual but far smaller primary tumor than what she started with.

In this instance, you may be considering stopping treatment but are concerned about doing so with evidence of disease still present.

Clinical trials of immunotherapy or chemoimmunotherapy have generally terminated treatment in nonprogressing patients after 2 years. We also know that some patients in early trials of immunotherapy stopped treatment after a fixed period of 1 or 2 years and continued to show no evidence of progression many years later.

The reason some patients experience this kind of success: Unlike the mechanism of action of conventional chemotherapy or targeted therapies, where ongoing treatment would be important to continue to exert an inhibitory effect, the active substrate of immunotherapy is the patient’s immune system, which can potentially have a self-sustaining efficacy beyond the stimulatory effect of the checkpoint inhibitor.

Though we don’t want to overtreat our patients, the question remains: Will patients do just as well off treatment, with the potential to resume as needed?

One trial directly addressed this question of stopping vs. continuing treatment in patients on immunotherapy. The CheckMate 153 trial, published in 2020, randomly assigned 252 previously treated patients who hadn’t demonstrated progression after 1 year on nivolumab to either discontinue nivolumab or continue nivolumab on an ongoing basis. The results were strongly in favor of ongoing therapy. Both progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who continued therapy: PFS of 24.7 months vs. 9.4 months and OS not reached vs. 32.5 months.

This finding is important, but there’s an important caveat. The study population included many heavily pretreated patients, but, in practice, immunotherapy has generally moved into the first-line setting, where we see dramatic responses in a significant subset of patients.

Even more recent data are emerging that may help us evaluate who will do well off therapy and who should continue treatment.

We now have a growing collection of long-term data on patients who are more likely to have good outcomes with immunotherapy, specifically those with high tumor programmed death-ligand 1 (PD-L1) expression (≥ 50%), from the KEYNOTE-024 trial. In this study, 39 of 151 (25.8%) patients assigned to pembrolizumab completed the planned maximum of 2 years of treatment, among whom 82.1% achieved an objective response; but, only 10% (4 patients) achieved a complete response. The proportion of patients without progression and remaining off therapy wasn’t reported, but the OS rate 3 years after completing treatment was 81.4%.

In addition, restarting immunotherapy after discontinuing appears to be a moderately effective strategy. In the KEYNOTE-024 trial, 12 patients received a second course of pembrolizumab because of disease progression a median of 15.2 months after discontinuing pembrolizumab. In this small cohort, eight of these patients (66.7%) were alive at the data cutoff, and six (50%) achieved stable disease.

Recently, we received additional insight in the follow-up from two chemoimmunotherapy trials that have most shaped my practice for patients with advanced NSCLC and any level of PD-L1 expression. These are the KEYNOTE-189 trial of platinum-pemetrexed with pembrolizumab vs. placebo in those with nonsquamous NSCLC, and the KEYNOTE-407 trial of carboplatin-taxane with pembrolizumab vs. placebo in patients with advanced squamous NSCLC. The National Comprehensive Cancer Network has designated each as a “preferred regimen” for patients with advanced NSCLC.

Both regimens have demonstrated sustained efficacy benefits with prolonged follow-up, including significantly superior objective response rate, PFS, and OS with the addition of pembrolizumab. These findings merely cemented the role of these regimens in our practice, but the trials also reported on the cohort of patients who completed 35 cycles of treatment over 2 years then discontinued therapy. In both, the majority of patients showed an objective response (86% in KEYNOTE-189 and 90% in KEYNOTE-407), with most patients alive at 3 years after 2 years of treatment (71.9% in KEYNOTE-189 and 69.5% in KEYNOTE-407). In addition, the proportion of patients alive without disease progression or subsequent therapy was notable – 40.4% in KEYNOTE-189 and 43.6% KEYNOTE-407.

How should we interpret these data for the patient who is in the exam room with us?

The short answer is that we don’t know. I see this as a half-empty, half-full conundrum.

I’m disappointed that more patients who responded for 2 years will experience disease progression in the 1-3 years that follow. This signals that their immune systems have not perpetuated their initial response over the long-term. But these patients may have demonstrated disease progression even if they had continued therapy.

We also know that some patients can be rechallenged and will respond again. Some of these patients will show stable disease, whereas others will progress with repeat treatment. I would love to be able to better predict which patients are destined to do well without treatment vs. those who benefit from treatment beyond 2 years.

Might the level of PD-L1 expression tell us? Can PET imaging discriminate those with residual hypermetabolism who may need continued treatment from those with no residual uptake who could be spared it? Would serial measurement of circulating tumor DNA (ctDNA) in responding patients identify when they have achieved a point of diminishing returns, potentially indicating that some can safely discontinue treatment after 2 years, whereas others need to continue to suppress on prolonged maintenance therapy?

These questions have yet to be studied systematically. In the meantime, I take an individualized approach with my patients facing this decision. Some have experienced escalating arthralgias and myalgias, cost concerns, or other issues related to immunotherapy that may dissuade us from continuing treatment. But several others have been grateful to continue with their treatment, hesitant to do anything that could change the path of their disease.

In my patients who tolerate therapy well, I’m more worried about potential undertreatment than overtreatment. I tend to favor having my patients continue therapy in the absence of problematic toxicity or practical challenges. There is certainly room for debate here while we await data to better guide these decisions. How do you approach these patients?

Dr. West is Clinical Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

A version of this article first appeared on Medscape.com.

It’s a “champagne problem” many of us have encountered over the past few years in the clinic.

A patient with advanced non–small cell lung cancer (NSCLC) is fortunate enough to continue to do well for 2 years on ongoing pembrolizumab or perhaps pemetrexed and pembrolizumab as maintenance therapy. The latest CT shows a residual but far smaller primary tumor than what she started with.

In this instance, you may be considering stopping treatment but are concerned about doing so with evidence of disease still present.

Clinical trials of immunotherapy or chemoimmunotherapy have generally terminated treatment in nonprogressing patients after 2 years. We also know that some patients in early trials of immunotherapy stopped treatment after a fixed period of 1 or 2 years and continued to show no evidence of progression many years later.

The reason some patients experience this kind of success: Unlike the mechanism of action of conventional chemotherapy or targeted therapies, where ongoing treatment would be important to continue to exert an inhibitory effect, the active substrate of immunotherapy is the patient’s immune system, which can potentially have a self-sustaining efficacy beyond the stimulatory effect of the checkpoint inhibitor.

Though we don’t want to overtreat our patients, the question remains: Will patients do just as well off treatment, with the potential to resume as needed?

One trial directly addressed this question of stopping vs. continuing treatment in patients on immunotherapy. The CheckMate 153 trial, published in 2020, randomly assigned 252 previously treated patients who hadn’t demonstrated progression after 1 year on nivolumab to either discontinue nivolumab or continue nivolumab on an ongoing basis. The results were strongly in favor of ongoing therapy. Both progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who continued therapy: PFS of 24.7 months vs. 9.4 months and OS not reached vs. 32.5 months.

This finding is important, but there’s an important caveat. The study population included many heavily pretreated patients, but, in practice, immunotherapy has generally moved into the first-line setting, where we see dramatic responses in a significant subset of patients.

Even more recent data are emerging that may help us evaluate who will do well off therapy and who should continue treatment.

We now have a growing collection of long-term data on patients who are more likely to have good outcomes with immunotherapy, specifically those with high tumor programmed death-ligand 1 (PD-L1) expression (≥ 50%), from the KEYNOTE-024 trial. In this study, 39 of 151 (25.8%) patients assigned to pembrolizumab completed the planned maximum of 2 years of treatment, among whom 82.1% achieved an objective response; but, only 10% (4 patients) achieved a complete response. The proportion of patients without progression and remaining off therapy wasn’t reported, but the OS rate 3 years after completing treatment was 81.4%.

In addition, restarting immunotherapy after discontinuing appears to be a moderately effective strategy. In the KEYNOTE-024 trial, 12 patients received a second course of pembrolizumab because of disease progression a median of 15.2 months after discontinuing pembrolizumab. In this small cohort, eight of these patients (66.7%) were alive at the data cutoff, and six (50%) achieved stable disease.

Recently, we received additional insight in the follow-up from two chemoimmunotherapy trials that have most shaped my practice for patients with advanced NSCLC and any level of PD-L1 expression. These are the KEYNOTE-189 trial of platinum-pemetrexed with pembrolizumab vs. placebo in those with nonsquamous NSCLC, and the KEYNOTE-407 trial of carboplatin-taxane with pembrolizumab vs. placebo in patients with advanced squamous NSCLC. The National Comprehensive Cancer Network has designated each as a “preferred regimen” for patients with advanced NSCLC.

Both regimens have demonstrated sustained efficacy benefits with prolonged follow-up, including significantly superior objective response rate, PFS, and OS with the addition of pembrolizumab. These findings merely cemented the role of these regimens in our practice, but the trials also reported on the cohort of patients who completed 35 cycles of treatment over 2 years then discontinued therapy. In both, the majority of patients showed an objective response (86% in KEYNOTE-189 and 90% in KEYNOTE-407), with most patients alive at 3 years after 2 years of treatment (71.9% in KEYNOTE-189 and 69.5% in KEYNOTE-407). In addition, the proportion of patients alive without disease progression or subsequent therapy was notable – 40.4% in KEYNOTE-189 and 43.6% KEYNOTE-407.

How should we interpret these data for the patient who is in the exam room with us?

The short answer is that we don’t know. I see this as a half-empty, half-full conundrum.

I’m disappointed that more patients who responded for 2 years will experience disease progression in the 1-3 years that follow. This signals that their immune systems have not perpetuated their initial response over the long-term. But these patients may have demonstrated disease progression even if they had continued therapy.

We also know that some patients can be rechallenged and will respond again. Some of these patients will show stable disease, whereas others will progress with repeat treatment. I would love to be able to better predict which patients are destined to do well without treatment vs. those who benefit from treatment beyond 2 years.

Might the level of PD-L1 expression tell us? Can PET imaging discriminate those with residual hypermetabolism who may need continued treatment from those with no residual uptake who could be spared it? Would serial measurement of circulating tumor DNA (ctDNA) in responding patients identify when they have achieved a point of diminishing returns, potentially indicating that some can safely discontinue treatment after 2 years, whereas others need to continue to suppress on prolonged maintenance therapy?

These questions have yet to be studied systematically. In the meantime, I take an individualized approach with my patients facing this decision. Some have experienced escalating arthralgias and myalgias, cost concerns, or other issues related to immunotherapy that may dissuade us from continuing treatment. But several others have been grateful to continue with their treatment, hesitant to do anything that could change the path of their disease.

In my patients who tolerate therapy well, I’m more worried about potential undertreatment than overtreatment. I tend to favor having my patients continue therapy in the absence of problematic toxicity or practical challenges. There is certainly room for debate here while we await data to better guide these decisions. How do you approach these patients?

Dr. West is Clinical Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

A version of this article first appeared on Medscape.com.

Scans of the lungs of pot users have turned up an alarming surprise: Regular smokers of marijuana appear to be at greater risk for lung damage than are people who smoke tobacco alone.

“There’s a public perception that marijuana is safe,” said Giselle Revah, MD, a radiologist at the University of Ottawa. “This study is raising concern that this might not be true.”

Dr. Revah said she can often tell immediately if a CT scan is from a heavy or long-time cigarette smoker. But with the legalization and increased use of marijuana in Canada and many U.S. states, she began to wonder what cannabis use does to the lungs and whether she would be able to differentiate its effects from those of cigarette smoking.

She and her colleagues retrospectively examined chest CT scans from 56 marijuana smokers and compared them to scans of 57 nonsmokers and 33 users of tobacco alone.

Emphysema was significantly more common among marijuana smokers (75%) than among nonsmokers (5%). When matched for age and sex, 93% of marijuana smokers had emphysema, vs. 67% of those who smoked tobacco only (P = .009).

Without age matching, rates of emphysema remained slightly higher among the marijuana users (75% vs. 67%), although the difference was no longer statistically significant. Yet more than 40% of the marijuana group was younger than 50 years, and all of the tobacco-only users were 50 or older – meaning that marijuana smokers may develop lung damage earlier or with less exposure, Dr. Revah said.

Dr. Revah added that her colleagues in family medicine have said the findings match their clinical experience. “In their practices, they have younger patients with emphysema,” she said.

Marijuana smokers also showed higher rates of airway inflammation, including bronchial thickening, bronchiectasis, and mucoid impaction, with and without sex- and age-matching, the researchers found.

The findings are “not even a little bit surprising,” according to Alan Kaplan, MD, a family physician in Ontario who has expertise in respiratory health. He is the author of a 2021 review on cannabis and lung health.

In an editorial accompanying the journal article by Dr. Revah and colleagues , pulmonary experts noted that the new data give context to a recent uptick in referrals for nontraumatic pneumothorax. The authors said they had received 22 of these referrals during the past 2 years but that they had received only 6 between 2012 and 2020. “Many, but not all, of these patients have a documented history of marijuana use,” they wrote.

One reason for the additional damage may be the way marijuana is inhaled, Dr. Kaplan said. Marijuana smokers “take a big breath in, and they really push it into lungs and hold pressure on it, which may actually cause alveoli to distend over time.”

Because most marijuana smokers in the study also smoked cigarettes, whether the observed damage was caused by marijuana alone or occurred through a synergy with tobacco is impossible to discern, Dr. Revah said.

Still, the results are striking, she said, because the marijuana group was compared to tobacco users who had an extensive smoking history – 25 to 100 pack-years – and who were from a high-risk lung cancer screening program.

Dr. Revah and her colleagues are now conducting a larger, prospective study to see whether they can confirm their findings.

“The message to physicians is to ask about cannabis smoking,” Dr. Kaplan said. In the past, people have been reluctant to admit to using cannabis. Even with legalization, they may be slow to tell their physicians. But clinicians should still try to identify frequent users, especially those who are predisposed for lung conditions. If they intend to use the drug, the advice should be, “There are safer ways to use cannabis,” he said.

Dr. Revah and Dr. Kaplan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Scans of the lungs of pot users have turned up an alarming surprise: Regular smokers of marijuana appear to be at greater risk for lung damage than are people who smoke tobacco alone.

“There’s a public perception that marijuana is safe,” said Giselle Revah, MD, a radiologist at the University of Ottawa. “This study is raising concern that this might not be true.”

Dr. Revah said she can often tell immediately if a CT scan is from a heavy or long-time cigarette smoker. But with the legalization and increased use of marijuana in Canada and many U.S. states, she began to wonder what cannabis use does to the lungs and whether she would be able to differentiate its effects from those of cigarette smoking.

She and her colleagues retrospectively examined chest CT scans from 56 marijuana smokers and compared them to scans of 57 nonsmokers and 33 users of tobacco alone.

Emphysema was significantly more common among marijuana smokers (75%) than among nonsmokers (5%). When matched for age and sex, 93% of marijuana smokers had emphysema, vs. 67% of those who smoked tobacco only (P = .009).

Without age matching, rates of emphysema remained slightly higher among the marijuana users (75% vs. 67%), although the difference was no longer statistically significant. Yet more than 40% of the marijuana group was younger than 50 years, and all of the tobacco-only users were 50 or older – meaning that marijuana smokers may develop lung damage earlier or with less exposure, Dr. Revah said.

Dr. Revah added that her colleagues in family medicine have said the findings match their clinical experience. “In their practices, they have younger patients with emphysema,” she said.

Marijuana smokers also showed higher rates of airway inflammation, including bronchial thickening, bronchiectasis, and mucoid impaction, with and without sex- and age-matching, the researchers found.

The findings are “not even a little bit surprising,” according to Alan Kaplan, MD, a family physician in Ontario who has expertise in respiratory health. He is the author of a 2021 review on cannabis and lung health.

In an editorial accompanying the journal article by Dr. Revah and colleagues , pulmonary experts noted that the new data give context to a recent uptick in referrals for nontraumatic pneumothorax. The authors said they had received 22 of these referrals during the past 2 years but that they had received only 6 between 2012 and 2020. “Many, but not all, of these patients have a documented history of marijuana use,” they wrote.

One reason for the additional damage may be the way marijuana is inhaled, Dr. Kaplan said. Marijuana smokers “take a big breath in, and they really push it into lungs and hold pressure on it, which may actually cause alveoli to distend over time.”

Because most marijuana smokers in the study also smoked cigarettes, whether the observed damage was caused by marijuana alone or occurred through a synergy with tobacco is impossible to discern, Dr. Revah said.

Still, the results are striking, she said, because the marijuana group was compared to tobacco users who had an extensive smoking history – 25 to 100 pack-years – and who were from a high-risk lung cancer screening program.

Dr. Revah and her colleagues are now conducting a larger, prospective study to see whether they can confirm their findings.

“The message to physicians is to ask about cannabis smoking,” Dr. Kaplan said. In the past, people have been reluctant to admit to using cannabis. Even with legalization, they may be slow to tell their physicians. But clinicians should still try to identify frequent users, especially those who are predisposed for lung conditions. If they intend to use the drug, the advice should be, “There are safer ways to use cannabis,” he said.

Dr. Revah and Dr. Kaplan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Scans of the lungs of pot users have turned up an alarming surprise: Regular smokers of marijuana appear to be at greater risk for lung damage than are people who smoke tobacco alone.

“There’s a public perception that marijuana is safe,” said Giselle Revah, MD, a radiologist at the University of Ottawa. “This study is raising concern that this might not be true.”

Dr. Revah said she can often tell immediately if a CT scan is from a heavy or long-time cigarette smoker. But with the legalization and increased use of marijuana in Canada and many U.S. states, she began to wonder what cannabis use does to the lungs and whether she would be able to differentiate its effects from those of cigarette smoking.

She and her colleagues retrospectively examined chest CT scans from 56 marijuana smokers and compared them to scans of 57 nonsmokers and 33 users of tobacco alone.

Emphysema was significantly more common among marijuana smokers (75%) than among nonsmokers (5%). When matched for age and sex, 93% of marijuana smokers had emphysema, vs. 67% of those who smoked tobacco only (P = .009).

Without age matching, rates of emphysema remained slightly higher among the marijuana users (75% vs. 67%), although the difference was no longer statistically significant. Yet more than 40% of the marijuana group was younger than 50 years, and all of the tobacco-only users were 50 or older – meaning that marijuana smokers may develop lung damage earlier or with less exposure, Dr. Revah said.

Dr. Revah added that her colleagues in family medicine have said the findings match their clinical experience. “In their practices, they have younger patients with emphysema,” she said.

Marijuana smokers also showed higher rates of airway inflammation, including bronchial thickening, bronchiectasis, and mucoid impaction, with and without sex- and age-matching, the researchers found.

The findings are “not even a little bit surprising,” according to Alan Kaplan, MD, a family physician in Ontario who has expertise in respiratory health. He is the author of a 2021 review on cannabis and lung health.

In an editorial accompanying the journal article by Dr. Revah and colleagues , pulmonary experts noted that the new data give context to a recent uptick in referrals for nontraumatic pneumothorax. The authors said they had received 22 of these referrals during the past 2 years but that they had received only 6 between 2012 and 2020. “Many, but not all, of these patients have a documented history of marijuana use,” they wrote.

One reason for the additional damage may be the way marijuana is inhaled, Dr. Kaplan said. Marijuana smokers “take a big breath in, and they really push it into lungs and hold pressure on it, which may actually cause alveoli to distend over time.”

Because most marijuana smokers in the study also smoked cigarettes, whether the observed damage was caused by marijuana alone or occurred through a synergy with tobacco is impossible to discern, Dr. Revah said.

Still, the results are striking, she said, because the marijuana group was compared to tobacco users who had an extensive smoking history – 25 to 100 pack-years – and who were from a high-risk lung cancer screening program.

Dr. Revah and her colleagues are now conducting a larger, prospective study to see whether they can confirm their findings.

“The message to physicians is to ask about cannabis smoking,” Dr. Kaplan said. In the past, people have been reluctant to admit to using cannabis. Even with legalization, they may be slow to tell their physicians. But clinicians should still try to identify frequent users, especially those who are predisposed for lung conditions. If they intend to use the drug, the advice should be, “There are safer ways to use cannabis,” he said.

Dr. Revah and Dr. Kaplan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.