Cancer

Many patients with cancer, as well as doctors in fields other than oncology, are unaware of just how much progress has been made in recent years in the treatment of cancer, particularly with immunotherapy.

This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.

The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.

When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.

Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.

“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.

After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”

Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.

Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.

He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.

“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.

That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.

For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
 

Findings from the patient survey

It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.

“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients

The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.

The survey asked them about how immunotherapy works, what it costs, and its side effects.

Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”

Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.

“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.

A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.

“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.

Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
 

Results of the doctor survey

The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.

Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).

Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.

Both groups of doctors had a hard time estimating the survival of common cancers.

Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.

However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.

“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.

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

Many patients with cancer, as well as doctors in fields other than oncology, are unaware of just how much progress has been made in recent years in the treatment of cancer, particularly with immunotherapy.

This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.

The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.

When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.

Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.

“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.

After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”

Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.

Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.

He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.

“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.

That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.

For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
 

Findings from the patient survey

It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.

“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients

The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.

The survey asked them about how immunotherapy works, what it costs, and its side effects.

Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”

Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.

“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.

A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.

“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.

Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
 

Results of the doctor survey

The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.

Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).

Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.

Both groups of doctors had a hard time estimating the survival of common cancers.

Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.

However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.

“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.

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

Many patients with cancer, as well as doctors in fields other than oncology, are unaware of just how much progress has been made in recent years in the treatment of cancer, particularly with immunotherapy.

This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.

The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.

When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.

Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.

“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.

After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”

Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.

Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.

He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.

“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.

That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.

For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
 

Findings from the patient survey

It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.

“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients

The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.

The survey asked them about how immunotherapy works, what it costs, and its side effects.

Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”

Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.

“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.

A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.

“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.

Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
 

Results of the doctor survey

The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.

Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).

Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.

Both groups of doctors had a hard time estimating the survival of common cancers.

Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.

However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.

“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.

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

Racial and ethnic disparities persist in the use of Mohs surgery to treat dermatofibrosarcoma protuberans, according to the results of a retrospective cohort study of more than 2,000 patients.

Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.

In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.

Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”

In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.

The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.

“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Racial and ethnic disparities persist in the use of Mohs surgery to treat dermatofibrosarcoma protuberans, according to the results of a retrospective cohort study of more than 2,000 patients.

Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.

In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.

Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”

In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.

The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.

“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Racial and ethnic disparities persist in the use of Mohs surgery to treat dermatofibrosarcoma protuberans, according to the results of a retrospective cohort study of more than 2,000 patients.

Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.

In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.

Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”

In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.

The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.

“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

The U.S. Food and Drug Administration has granted accelerated approval to tisotumab vedotin-tftv (Tivdak, Seagen/Genmab) for the treatment of adult patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy.

There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.

In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”

“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.

Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
 

Details of clinical trial data

The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.

The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.

All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.

The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.

The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.

Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.

Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.

The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
 

Confirmatory trial underway

Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.

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

The U.S. Food and Drug Administration has granted accelerated approval to tisotumab vedotin-tftv (Tivdak, Seagen/Genmab) for the treatment of adult patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy.

There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.

In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”

“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.

Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
 

Details of clinical trial data

The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.

The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.

All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.

The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.

The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.

Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.

Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.

The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
 

Confirmatory trial underway

Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.

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

The U.S. Food and Drug Administration has granted accelerated approval to tisotumab vedotin-tftv (Tivdak, Seagen/Genmab) for the treatment of adult patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy.

There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.

In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”

“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.

Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
 

Details of clinical trial data

The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.

The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.

All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.

The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.

The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.

Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.

Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.

The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
 

Confirmatory trial underway

Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.

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

Foregoing chemotherapy in favor of cancer immunotherapy (CIT) alone for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) and high programmed death–ligand 1 (PD-L1) expression did not impact survival outcomes in a retrospective cohort of U.S. patients – except in a subgroup of nonsmokers.

Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).

However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.

She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.

Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.

The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.

“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.

The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.

Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.

Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.

For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.

The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.

“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.

Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.

Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.

This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.

sworcester@mdedge.com

Foregoing chemotherapy in favor of cancer immunotherapy (CIT) alone for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) and high programmed death–ligand 1 (PD-L1) expression did not impact survival outcomes in a retrospective cohort of U.S. patients – except in a subgroup of nonsmokers.

Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).

However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.

She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.

Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.

The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.

“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.

The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.

Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.

Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.

For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.

The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.

“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.

Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.

Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.

This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.

sworcester@mdedge.com

Foregoing chemotherapy in favor of cancer immunotherapy (CIT) alone for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) and high programmed death–ligand 1 (PD-L1) expression did not impact survival outcomes in a retrospective cohort of U.S. patients – except in a subgroup of nonsmokers.

Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).

However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.

She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.

Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.

The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.

“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.

The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.

Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.

Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.

For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.

The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.

“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.

Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.

Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.

This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.

sworcester@mdedge.com

Community outreach coordinators identified Veterans who were not aware of their entitlement to service-connected benefits. Veterans were also unaware of the importance of adding new presumptive diagnoses to their existing service connection and were unaware of new conditions that were added to the presumptive lists. Many Veterans, unaware of the Agent Orange/Camp Lejeune presumptive conditions, were paying out of pocket for their oncology care. A project was developed between community outreach and oncology to identify, and contact Veterans newly diagnosed with cancers on the presumptive list for Vietnam and Camp Lejeune. The goals for the project were to: Increase presumptive condition awareness, assist Veterans in navigating the VHA, VBA and VSC (Veteran Service Commission) and provide a VA resource for the Veterans for assistance. Oncology team reviewed the cancer registry each month and identified Veterans who served during the Vietnam Era or the Marine Corps and contacted them to screen for military history. If a Veteran met the time and location qualifications, the Veteran was referred to the community outreach coordinators. The coordinators then further screened the Veterans for eligibility, assisted the Veterans in initiating their claims applications and connected the Veterans with their local VSC. At the six month follow up, 74 Veterans had been referred to community outreach, and 16 Veterans had received 100% service connection. It is important to note, the benefits application process can take several months to complete under normal circumstances. Since implementation the project has been revised. The project team developed mailers to alert Veterans of: Potential benefits eligibility, importance for filing claims, contact information for their local VSC and contact information for VA Outreach for additional assistance. Informatics was recruited to assist with identifying Veterans who met the service criteria and providing their addresses. The Veterans identified were then sent mailers, which expedited the process, allowing the project team to reach more Veterans in a shorter timeframe. Since project initiation, 74 Veterans were contacted directly by outreach coordinators, 273 mailers have been sent to potentially eligible Veterans, and 34 have received 100% service connection to date. al center will continue this practice moving forward.

Community outreach coordinators identified Veterans who were not aware of their entitlement to service-connected benefits. Veterans were also unaware of the importance of adding new presumptive diagnoses to their existing service connection and were unaware of new conditions that were added to the presumptive lists. Many Veterans, unaware of the Agent Orange/Camp Lejeune presumptive conditions, were paying out of pocket for their oncology care. A project was developed between community outreach and oncology to identify, and contact Veterans newly diagnosed with cancers on the presumptive list for Vietnam and Camp Lejeune. The goals for the project were to: Increase presumptive condition awareness, assist Veterans in navigating the VHA, VBA and VSC (Veteran Service Commission) and provide a VA resource for the Veterans for assistance. Oncology team reviewed the cancer registry each month and identified Veterans who served during the Vietnam Era or the Marine Corps and contacted them to screen for military history. If a Veteran met the time and location qualifications, the Veteran was referred to the community outreach coordinators. The coordinators then further screened the Veterans for eligibility, assisted the Veterans in initiating their claims applications and connected the Veterans with their local VSC. At the six month follow up, 74 Veterans had been referred to community outreach, and 16 Veterans had received 100% service connection. It is important to note, the benefits application process can take several months to complete under normal circumstances. Since implementation the project has been revised. The project team developed mailers to alert Veterans of: Potential benefits eligibility, importance for filing claims, contact information for their local VSC and contact information for VA Outreach for additional assistance. Informatics was recruited to assist with identifying Veterans who met the service criteria and providing their addresses. The Veterans identified were then sent mailers, which expedited the process, allowing the project team to reach more Veterans in a shorter timeframe. Since project initiation, 74 Veterans were contacted directly by outreach coordinators, 273 mailers have been sent to potentially eligible Veterans, and 34 have received 100% service connection to date. al center will continue this practice moving forward.

Community outreach coordinators identified Veterans who were not aware of their entitlement to service-connected benefits. Veterans were also unaware of the importance of adding new presumptive diagnoses to their existing service connection and were unaware of new conditions that were added to the presumptive lists. Many Veterans, unaware of the Agent Orange/Camp Lejeune presumptive conditions, were paying out of pocket for their oncology care. A project was developed between community outreach and oncology to identify, and contact Veterans newly diagnosed with cancers on the presumptive list for Vietnam and Camp Lejeune. The goals for the project were to: Increase presumptive condition awareness, assist Veterans in navigating the VHA, VBA and VSC (Veteran Service Commission) and provide a VA resource for the Veterans for assistance. Oncology team reviewed the cancer registry each month and identified Veterans who served during the Vietnam Era or the Marine Corps and contacted them to screen for military history. If a Veteran met the time and location qualifications, the Veteran was referred to the community outreach coordinators. The coordinators then further screened the Veterans for eligibility, assisted the Veterans in initiating their claims applications and connected the Veterans with their local VSC. At the six month follow up, 74 Veterans had been referred to community outreach, and 16 Veterans had received 100% service connection. It is important to note, the benefits application process can take several months to complete under normal circumstances. Since implementation the project has been revised. The project team developed mailers to alert Veterans of: Potential benefits eligibility, importance for filing claims, contact information for their local VSC and contact information for VA Outreach for additional assistance. Informatics was recruited to assist with identifying Veterans who met the service criteria and providing their addresses. The Veterans identified were then sent mailers, which expedited the process, allowing the project team to reach more Veterans in a shorter timeframe. Since project initiation, 74 Veterans were contacted directly by outreach coordinators, 273 mailers have been sent to potentially eligible Veterans, and 34 have received 100% service connection to date. al center will continue this practice moving forward.

Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.

Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.

“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”

Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.

The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.

“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”

Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”

The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”

Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”

The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”

However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”

“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”

She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.

Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”

No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.

Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.

Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.

“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”

Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.

The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.

“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”

Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”

The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”

Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”

The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”

However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”

“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”

She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.

Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”

No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.

Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.

Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.

“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”

Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.

The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.

“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”

Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”

The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”

Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”

The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”

However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”

“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”

She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.

Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”

No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.

The U.S. Food and Drug Administration has granted an accelerated approval to mobocertinib (Exkivity, Takeda) for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR Exon 20 insertion mutation detected on an FDA-approved test.

Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer.

“EGFR Exon 20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute, Boston, in a press statement from the maker, Takeda.

“The approval of [mobocertinib] marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses,” Dr. Jänne added.

According to the company, EGFR Exon 20 insertion+ NSCLC makes up approximately 1%-2% of patients with NSCLC and is more common in Asian populations compared with Western populations.

The new approval is based on overall response rate (ORR) and duration of response (DoR) results from a phase 1/2 trial consisting of 114 patients with EGFR Exon 20 insertion+ NSCLC who received prior platinum-based therapy and were treated with the 160-mg dose.

Per an independent review committee, mobocertinib demonstrated a confirmed ORR of 28% and a median DoR of 17.5 months.

Median overall survival was 24 months and median progression-free survival was 7.3 months.

The FDA-approved next-generation sequencing (NGS) companion diagnostic for mobocertinib is Thermo Fisher Scientific’s Oncomine Dx Target Test, which identifies NSCLC patients with EGFR Exon 20 insertions.

“NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon 20 insertions,” according to the company.

Results from the phase 1/2 trial used in the FDA approval were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The most common adverse reactions (greater than 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company.

The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

“Patients with EGFR Exon 20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at the International Cancer Advocacy Network, in the press statement.

The FDA review was conducted under Project Orbis, an FDA initiative that enables concurrent submission and review of oncology products among international partners.

The new drug was also granted priority review and received breakthrough therapy, fast track, and orphan drug designations from the FDA.

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

The U.S. Food and Drug Administration has granted an accelerated approval to mobocertinib (Exkivity, Takeda) for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR Exon 20 insertion mutation detected on an FDA-approved test.

Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer.

“EGFR Exon 20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute, Boston, in a press statement from the maker, Takeda.

“The approval of [mobocertinib] marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses,” Dr. Jänne added.

According to the company, EGFR Exon 20 insertion+ NSCLC makes up approximately 1%-2% of patients with NSCLC and is more common in Asian populations compared with Western populations.

The new approval is based on overall response rate (ORR) and duration of response (DoR) results from a phase 1/2 trial consisting of 114 patients with EGFR Exon 20 insertion+ NSCLC who received prior platinum-based therapy and were treated with the 160-mg dose.

Per an independent review committee, mobocertinib demonstrated a confirmed ORR of 28% and a median DoR of 17.5 months.

Median overall survival was 24 months and median progression-free survival was 7.3 months.

The FDA-approved next-generation sequencing (NGS) companion diagnostic for mobocertinib is Thermo Fisher Scientific’s Oncomine Dx Target Test, which identifies NSCLC patients with EGFR Exon 20 insertions.

“NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon 20 insertions,” according to the company.

Results from the phase 1/2 trial used in the FDA approval were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The most common adverse reactions (greater than 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company.

The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

“Patients with EGFR Exon 20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at the International Cancer Advocacy Network, in the press statement.

The FDA review was conducted under Project Orbis, an FDA initiative that enables concurrent submission and review of oncology products among international partners.

The new drug was also granted priority review and received breakthrough therapy, fast track, and orphan drug designations from the FDA.

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

The U.S. Food and Drug Administration has granted an accelerated approval to mobocertinib (Exkivity, Takeda) for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

The drug is limited to use in patients whose disease has progressed on or after platinum-based chemotherapy and who have had the EGFR Exon 20 insertion mutation detected on an FDA-approved test.

Mobocertinib is the first oral tyrosine kinase inhibitor (TKI) specifically designed to target these mutations, which are less common than the more predominant EGFR mutations in this lung cancer.

“EGFR Exon 20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute, Boston, in a press statement from the maker, Takeda.

“The approval of [mobocertinib] marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses,” Dr. Jänne added.

According to the company, EGFR Exon 20 insertion+ NSCLC makes up approximately 1%-2% of patients with NSCLC and is more common in Asian populations compared with Western populations.

The new approval is based on overall response rate (ORR) and duration of response (DoR) results from a phase 1/2 trial consisting of 114 patients with EGFR Exon 20 insertion+ NSCLC who received prior platinum-based therapy and were treated with the 160-mg dose.

Per an independent review committee, mobocertinib demonstrated a confirmed ORR of 28% and a median DoR of 17.5 months.

Median overall survival was 24 months and median progression-free survival was 7.3 months.

The FDA-approved next-generation sequencing (NGS) companion diagnostic for mobocertinib is Thermo Fisher Scientific’s Oncomine Dx Target Test, which identifies NSCLC patients with EGFR Exon 20 insertions.

“NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon 20 insertions,” according to the company.

Results from the phase 1/2 trial used in the FDA approval were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The most common adverse reactions (greater than 20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain, according to the company.

The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings and precautions for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

“Patients with EGFR Exon 20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at the International Cancer Advocacy Network, in the press statement.

The FDA review was conducted under Project Orbis, an FDA initiative that enables concurrent submission and review of oncology products among international partners.

The new drug was also granted priority review and received breakthrough therapy, fast track, and orphan drug designations from the FDA.

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

A review of patients with advanced cancer and poor performance status (PS) has shown that objective responses to immunotherapy are rare and that overall survival (OS) is extremely limited. The findings have prompted an expert to argue against the use of immunotherapy for such patients, who may have little time left and very little chance of benefiting.

“It is quite clear from clinical practice that most patients with limited PS do very poorly and do not benefit from immune check point inhibitors (ICI),” Jason Luke, MD, UPMC Hillman Cancer Center and the University of Pittsburgh, said in an email.

“So, my strong opinion is that patients should not be getting an immunotherapy just because it might not cause as many side effects as chemotherapy,” he added.

“Instead of giving an immunotherapy with little chance of success, patients and families deserve to have a direct conversation about what realistic expectations [might be] and how we as the oncology community can support them to achieve whatever their personal goals are in the time that they have left,” he emphasized.

Dr. Luke was the lead author of an editorial in which he commented on the study. Both the study and the editorial were published online in JCO Oncology Practice.
 

Variety of cancers

The study was conducted by Mridula Krishnan, MD, Nebraska Medicine Fred and Pamela Buffett Cancer Center, Omaha, Nebraska, and colleagues.

The team reviewed 257 patients who had been treated with either a programmed cell death protein–1 inhibitor or programmed cell death–ligand-1 inhibitor for a variety of advanced cancers. The drugs included pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentique), durvalumab (Imfinzi), and avelumab (Bavencio).

Most of the patients (71%) had good PS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0-1 on initiation of immunotherapy; 29% of patients had poor PS, with an ECOG PS of greater than or equal to 2.

“The primary outcome was OS stratified by ECOG PS 0-1 versus ≥2,” note the authors. Across all tumor types, OS was superior for patients in the ECOG 0-1 PS group, the investigators note. The median OS was 12.6 months, compared with only 3.1 months for patients in the ECOG greater than or equal to 2 group (P < .001).

Moreover, overall response rates for patients with a poor PS were low. Only 8%, or 6 of 75 patients with an ECOG PS of greater than or equal to 2, achieved an objective response by RECIST criteria.

This compared to an overall response rate of 23% for patients with an ECOG PS of 0-1, the investigators note (P = .005).

Interestingly, the hospice referral rate for patients with a poor PS (67%) was similar to that of patients with a PS of 1-2 (61.9%), Dr. Krishnan and colleagues observe.

Those with a poor PS were more like to die in-hospital (28.6%) than were patients with a good PS (15.1%; P = .035). The authors point out that it is well known that outcomes with chemotherapy are worse among patients who experience a decline in functional reserve, owing to increased susceptibility to toxicity and complications.

“Regardless of age, patients with ECOG PS >2 usually have poor tolerability to chemotherapy, and this correlates with worse survival outcome,” they emphasize. There is as yet no clear guidance regarding the impact of PS on ICI treatment response, although “there should be,” Dr. Luke believes.

“In a patient with declining performance status, especially ECOG PS 3-4 but potentially 2 as well, there is little likelihood that the functional and immune reserve of the patient will be adequate to mount a robust antitumor response,” he elaborated.

“It’s not impossible, but trying for it should not come at the expense of engaging about end-of-life care and maximizing the palliative opportunities that many only have a short window of time in which to pursue,” he added.

Again, Dr. Luke strongly believes that just giving an ICI without engaging in a frank conversation with the patient and their families – which happens all too often, he feels – is absolutely not the way to go when treating patients with a poor PS and little time left.

“Patients and families might be better served by having a more direct and frank conversation about what the likelihood [is] that ICI therapy will actually do,” Dr. Luke stressed.

In their editorial, Dr. Luke and colleagues write: “Overall, we as an oncology community need to improve our communication with patients regarding goals of care and end-of-life considerations as opposed to reflexive treatment initiation,” he writes.

“Our duty, first and foremost, should focus on the person sitting in front of us – taking a step back may be the best way to move forward with compassionate care,” they add.

The authors and editorialists have disclosed no relevant financial relationships.

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

A review of patients with advanced cancer and poor performance status (PS) has shown that objective responses to immunotherapy are rare and that overall survival (OS) is extremely limited. The findings have prompted an expert to argue against the use of immunotherapy for such patients, who may have little time left and very little chance of benefiting.

“It is quite clear from clinical practice that most patients with limited PS do very poorly and do not benefit from immune check point inhibitors (ICI),” Jason Luke, MD, UPMC Hillman Cancer Center and the University of Pittsburgh, said in an email.

“So, my strong opinion is that patients should not be getting an immunotherapy just because it might not cause as many side effects as chemotherapy,” he added.

“Instead of giving an immunotherapy with little chance of success, patients and families deserve to have a direct conversation about what realistic expectations [might be] and how we as the oncology community can support them to achieve whatever their personal goals are in the time that they have left,” he emphasized.

Dr. Luke was the lead author of an editorial in which he commented on the study. Both the study and the editorial were published online in JCO Oncology Practice.
 

Variety of cancers

The study was conducted by Mridula Krishnan, MD, Nebraska Medicine Fred and Pamela Buffett Cancer Center, Omaha, Nebraska, and colleagues.

The team reviewed 257 patients who had been treated with either a programmed cell death protein–1 inhibitor or programmed cell death–ligand-1 inhibitor for a variety of advanced cancers. The drugs included pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentique), durvalumab (Imfinzi), and avelumab (Bavencio).

Most of the patients (71%) had good PS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0-1 on initiation of immunotherapy; 29% of patients had poor PS, with an ECOG PS of greater than or equal to 2.

“The primary outcome was OS stratified by ECOG PS 0-1 versus ≥2,” note the authors. Across all tumor types, OS was superior for patients in the ECOG 0-1 PS group, the investigators note. The median OS was 12.6 months, compared with only 3.1 months for patients in the ECOG greater than or equal to 2 group (P < .001).

Moreover, overall response rates for patients with a poor PS were low. Only 8%, or 6 of 75 patients with an ECOG PS of greater than or equal to 2, achieved an objective response by RECIST criteria.

This compared to an overall response rate of 23% for patients with an ECOG PS of 0-1, the investigators note (P = .005).

Interestingly, the hospice referral rate for patients with a poor PS (67%) was similar to that of patients with a PS of 1-2 (61.9%), Dr. Krishnan and colleagues observe.

Those with a poor PS were more like to die in-hospital (28.6%) than were patients with a good PS (15.1%; P = .035). The authors point out that it is well known that outcomes with chemotherapy are worse among patients who experience a decline in functional reserve, owing to increased susceptibility to toxicity and complications.

“Regardless of age, patients with ECOG PS >2 usually have poor tolerability to chemotherapy, and this correlates with worse survival outcome,” they emphasize. There is as yet no clear guidance regarding the impact of PS on ICI treatment response, although “there should be,” Dr. Luke believes.

“In a patient with declining performance status, especially ECOG PS 3-4 but potentially 2 as well, there is little likelihood that the functional and immune reserve of the patient will be adequate to mount a robust antitumor response,” he elaborated.

“It’s not impossible, but trying for it should not come at the expense of engaging about end-of-life care and maximizing the palliative opportunities that many only have a short window of time in which to pursue,” he added.

Again, Dr. Luke strongly believes that just giving an ICI without engaging in a frank conversation with the patient and their families – which happens all too often, he feels – is absolutely not the way to go when treating patients with a poor PS and little time left.

“Patients and families might be better served by having a more direct and frank conversation about what the likelihood [is] that ICI therapy will actually do,” Dr. Luke stressed.

In their editorial, Dr. Luke and colleagues write: “Overall, we as an oncology community need to improve our communication with patients regarding goals of care and end-of-life considerations as opposed to reflexive treatment initiation,” he writes.

“Our duty, first and foremost, should focus on the person sitting in front of us – taking a step back may be the best way to move forward with compassionate care,” they add.

The authors and editorialists have disclosed no relevant financial relationships.

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

A review of patients with advanced cancer and poor performance status (PS) has shown that objective responses to immunotherapy are rare and that overall survival (OS) is extremely limited. The findings have prompted an expert to argue against the use of immunotherapy for such patients, who may have little time left and very little chance of benefiting.

“It is quite clear from clinical practice that most patients with limited PS do very poorly and do not benefit from immune check point inhibitors (ICI),” Jason Luke, MD, UPMC Hillman Cancer Center and the University of Pittsburgh, said in an email.

“So, my strong opinion is that patients should not be getting an immunotherapy just because it might not cause as many side effects as chemotherapy,” he added.

“Instead of giving an immunotherapy with little chance of success, patients and families deserve to have a direct conversation about what realistic expectations [might be] and how we as the oncology community can support them to achieve whatever their personal goals are in the time that they have left,” he emphasized.

Dr. Luke was the lead author of an editorial in which he commented on the study. Both the study and the editorial were published online in JCO Oncology Practice.
 

Variety of cancers

The study was conducted by Mridula Krishnan, MD, Nebraska Medicine Fred and Pamela Buffett Cancer Center, Omaha, Nebraska, and colleagues.

The team reviewed 257 patients who had been treated with either a programmed cell death protein–1 inhibitor or programmed cell death–ligand-1 inhibitor for a variety of advanced cancers. The drugs included pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentique), durvalumab (Imfinzi), and avelumab (Bavencio).

Most of the patients (71%) had good PS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0-1 on initiation of immunotherapy; 29% of patients had poor PS, with an ECOG PS of greater than or equal to 2.

“The primary outcome was OS stratified by ECOG PS 0-1 versus ≥2,” note the authors. Across all tumor types, OS was superior for patients in the ECOG 0-1 PS group, the investigators note. The median OS was 12.6 months, compared with only 3.1 months for patients in the ECOG greater than or equal to 2 group (P < .001).

Moreover, overall response rates for patients with a poor PS were low. Only 8%, or 6 of 75 patients with an ECOG PS of greater than or equal to 2, achieved an objective response by RECIST criteria.

This compared to an overall response rate of 23% for patients with an ECOG PS of 0-1, the investigators note (P = .005).

Interestingly, the hospice referral rate for patients with a poor PS (67%) was similar to that of patients with a PS of 1-2 (61.9%), Dr. Krishnan and colleagues observe.

Those with a poor PS were more like to die in-hospital (28.6%) than were patients with a good PS (15.1%; P = .035). The authors point out that it is well known that outcomes with chemotherapy are worse among patients who experience a decline in functional reserve, owing to increased susceptibility to toxicity and complications.

“Regardless of age, patients with ECOG PS >2 usually have poor tolerability to chemotherapy, and this correlates with worse survival outcome,” they emphasize. There is as yet no clear guidance regarding the impact of PS on ICI treatment response, although “there should be,” Dr. Luke believes.

“In a patient with declining performance status, especially ECOG PS 3-4 but potentially 2 as well, there is little likelihood that the functional and immune reserve of the patient will be adequate to mount a robust antitumor response,” he elaborated.

“It’s not impossible, but trying for it should not come at the expense of engaging about end-of-life care and maximizing the palliative opportunities that many only have a short window of time in which to pursue,” he added.

Again, Dr. Luke strongly believes that just giving an ICI without engaging in a frank conversation with the patient and their families – which happens all too often, he feels – is absolutely not the way to go when treating patients with a poor PS and little time left.

“Patients and families might be better served by having a more direct and frank conversation about what the likelihood [is] that ICI therapy will actually do,” Dr. Luke stressed.

In their editorial, Dr. Luke and colleagues write: “Overall, we as an oncology community need to improve our communication with patients regarding goals of care and end-of-life considerations as opposed to reflexive treatment initiation,” he writes.

“Our duty, first and foremost, should focus on the person sitting in front of us – taking a step back may be the best way to move forward with compassionate care,” they add.

The authors and editorialists have disclosed no relevant financial relationships.

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

Another study has shown an association between antibiotic use and an increased risk for colon cancer.

The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.

Sheep purple/flickr/CC BY 2.0 /en.wikipedia/CC BY-SA 4.0

They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.

In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.

Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).

The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.

The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.

The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.

“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.

In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.

The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.

This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”

A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.

Details of the study findings

For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.

They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.

Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.

The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.

Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).

Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).

Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.

Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).

For distal colon cancer, the relationship was “close to null.”

There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.

The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.

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

Another study has shown an association between antibiotic use and an increased risk for colon cancer.

The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.

Sheep purple/flickr/CC BY 2.0 /en.wikipedia/CC BY-SA 4.0

They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.

In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.

Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).

The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.

The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.

The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.

“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.

In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.

The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.

This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”

A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.

Details of the study findings

For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.

They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.

Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.

The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.

Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).

Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).

Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.

Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).

For distal colon cancer, the relationship was “close to null.”

There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.

The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.

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

Another study has shown an association between antibiotic use and an increased risk for colon cancer.

The latest data come from a Swedish population study. Investigators analyzed data from more than 40,000 colorectal cancer patients and 200,000 cancer-free control persons.

Sheep purple/flickr/CC BY 2.0 /en.wikipedia/CC BY-SA 4.0

They found that moderate use of antibiotics increased the risk for proximal colon cancer by 9% and that very high antibiotic use increased the risk by 17%.

In contrast, the risk for rectal cancer was reduced by 4% with moderate use and 9% with very high use, but this association was confined to women.

Antibiotic use was categorized as no use (no reported use of antibiotics during the study period), low (use during a period of 1-10 days), moderate (11-60 days), high (61-180 days), and very high (>180 days).

The study, led by Sophia Harlid, PhD, department of radiation sciences, oncology, Umeå University, Sweden, was published online on Sept. 1 in the Journal of the National Cancer Institute.

The results complement findings from a recent study from Scotland, which found that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer but not rectal cancer by 49%.

The new data from Sweden “strengthen prior evidence and provide new insights into site-specific carcinogenesis as well as indirect support for the role of gut microbiota,” lead author Dr. Dr. Harlid commented in an interview.

“The positive associations between antibiotics use and proximal colon cancer began at the lowest level of antibiotics use, providing a potential justification for reducing antibiotics prescriptions in clinical practice,” she added.

In their article, the team suggests that the increased risk could be a result of antibiotics having a “disruptive effect” on the gut microbiome.

The finding of an increased risk for cancer in the proximal colon but not further along the alimentary tract “is consistent with a high microbial impact in the proximal colon and a decreasing concentration of short-chain fatty acids along the colon,” the authors comment.

This results “in higher bacterial activity, biofilm formation, and fermentation in the proximal compared with the distal colon and rectum.”

A further analysis showed that the use of quinolones and sulfonamides and/or trimethoprims was associated with an increased risk for proximal colon cancer, whereas use of nitrofurantoins, macrolides and/or lincosamides, and metronidazoles and/or tinidazoles was inversely associated with rectal cancer.

Details of the study findings

For their study, the team analyzed complete-population data from Swedish national registers for the period July 1, 2005 to Dec. 31, 2016.

They matched case patients who were diagnosed with colorectal cancer from Jan. 1, 2010 to Dec. 31, 2016 with cancer-free control persons in a 1:5 ratio. Data on antibiotic use were extracted from the Swedish Prescribed Drug Register.

Other variables, such as socioeconomic factors and health care utilization, were obtained from the Swedish Inpatient Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies.

The team identified 40,545 patients with colorectal cancer cases; there were 202,720 control persons. Just over half (52.9%) of the participants were men; the mean age at cancer diagnosis was 72 years. Among the cases, 36.4% were proximal colon cancers, 29.3% were distal colon cancers, and 33.0% rectal cancers.

Control patients were more likely to have been prescribed no antibiotics, at 22.4% versus 18.7% for case patients. Case patients were more likely than control persons to have used antibiotics for more than 2 months, at 20.8% versus 19.3% (P < .001).

Overall, antibiotic use was positively associated with colorectal cancer. In comparison with no use, the odds ratio for moderate use was 1.15; for very high use, it was 1.17 (P < .001 for trend).

Excluding all antibiotic use during the 2 years prior to a colorectal cancer diagnosis attenuated the association, such that it was no longer significant for very high use versus no antibiotic use.

Applying this cutoff to the remaining analyses, the team found that the dose-response relationship between antibiotic use and colorectal cancer was largely confined to proximal colon cancer, at an odds ratio of 1.09 for moderate use and 1.17 for very high use in comparison with no use (P < .001 for trend).

For distal colon cancer, the relationship was “close to null.”

There was a slight inverse relationship between rectal cancer and antibiotic use, at an odds rate of 0.96 for moderate use and 0.91 for very high use versus no use (P < .001 for trend). This association was found in women only, whereas the other associations were seen in both men and women.

The study was supported by the Lion’s Cancer Research Foundation, Umeå University, and Region Västerbotten. Dr. Harlid has disclosed no relevant financial relationships. Three coauthors report various relationships with industry, as noted in the original article.

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

Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.

These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.

These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).

Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.

Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.

Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.

These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.

“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.

The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.

Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.

This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.

Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.

Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.

The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.

“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.

However, she expressed concern that “with the telehealth visits, we can create some disparities.”

“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.

Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”

Impact on lung cancer clinical trials

The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.

Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.

The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).

The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.

The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).

Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).

Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).

“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.

Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.

This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).

Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).

The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.

Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.

The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.

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

Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.

These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.

These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).

Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.

Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.

Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.

These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.

“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.

The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.

Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.

This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.

Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.

Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.

The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.

“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.

However, she expressed concern that “with the telehealth visits, we can create some disparities.”

“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.

Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”

Impact on lung cancer clinical trials

The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.

Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.

The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).

The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.

The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).

Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).

Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).

“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.

Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.

This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).

Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).

The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.

Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.

The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.

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

Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.

These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.

These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).

Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.

Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.

Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.

These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.

“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.

The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.

Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.

This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.

Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.

Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.

The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.

“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.

However, she expressed concern that “with the telehealth visits, we can create some disparities.”

“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.

Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”

Impact on lung cancer clinical trials

The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.

Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.

The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).

The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.

The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).

Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).

Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).

“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.

Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.

This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).

Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).

The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.

Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.

The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.

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