User login
TRK inhibitor shows ‘striking’ activity, durability across diverse adult and pediatric cancers
CHICAGO – Larotrectinib, an oral inhibitor of tropomyosin receptor kinase (TRK), has durable efficacy across diverse adult and pediatric cancers that harbor a genetic aberration known as TRK fusion, finds an analysis of three trials reported at the annual meeting of the American Society of Clinical Oncology.
Fusion of a TRK gene with an unrelated gene leads to uncontrolled signaling in the TRK pathway, potentially causing tumor growth and addiction to this input, lead author David Hyman, MD, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York explained in a press briefing.
Dr. Hyman and his colleagues analyzed data from 55 patients having 17 discrete types of advanced cancer harboring TRK fusions who were treated with larotrectinib in phase I and II trials. Results showed an overall response rate of 76%, and the large majority of responses were still ongoing at 12 months.
“I believe these data support larotrectinib as a potential new standard of care for these patients,” he said. “However, I want to emphasize that really recognizing this benefit in the community will require that we test patients more universally for the presence of TRK fusions or other tumor-agnostic biomarkers, such as microsatellite instability.”
On the basis of these promising data, the drug’s manufacturer, Loxo Oncology, plans to submit a New Drug Application to the Food and Drug Administration later this year or early next year. Larotrectinib has already been granted both orphan drug designation (for drugs used to treat rare conditions) and breakthrough therapy designation (for drugs used to treat serious conditions showing greater efficacy than available therapies).
A randomized trial pitting larotrectinib against other therapies is unlikely given the low prevalence of TRK fusions, the lack of treatment options for the fairly heavily pretreated trial patients, and the drug’s impressive performance, according to Dr. Hyman.
“The efficacy is so striking that it really exceeds almost any existing standard of care for solid tumors,” he elaborated. “There is hardly any chemotherapy or targeted therapy that has a response rate or durability that looks like larotrectinib in these patients.”
Expert perspective
The data for larotrectinib “really bring us into a new era where treatment is truly based on mutation, not location,” said Sumanta Kumar Pal, MD, a medical oncologist at City of Hope, in Duarte, Calif. “When I was in training, which was not too long ago, it really would have been a pipe dream to think that we could have treated cancers independent of their site of origin. … With the data presented by Dr. Hyman for larotrectinib, we may now be poised to treat many cancers in a manner that is agnostic of their site of origin and that is instead based on molecular criteria.
TRK testing
Several next-generation sequencing–based tests already available clinically can pick up TRK fusions, Dr. Hyman pointed out. “But it is important for the ordering physician to understand whether the tests they are ordering includes fusion detection and, if it’s an option, to select it. Otherwise, they will not find TRK fusions.
“The list price for these tests is in the kind of low thousands of dollars, which equates essentially to a PET scan for the cancer patient,” he noted. In cancers where sequential single-gene testing is already being done as standard of care, there is “minimal” incremental cost of instead using comprehensive testing that would detect TRK fusions.
Oncologists should be aware that obtaining test results can take weeks, Dr. Hyman stressed. “My personal opinion is that this [testing] should be more broadly adopted and should be adopted at a point in the patient’s treatment … [so that they] don’t become too sick, as we see in our own experience as well, and don’t have an opportunity to be treated even when the test results come back positive. So I would generally advocate early testing.”
Study details
For the study, which was funded by Loxo Oncology, the investigators analyzed data from three trials in which patients with advanced TRK fusion–positive solid cancers received larotrectinib (LOXO-101): a phase I trial among 8 adult patients, a phase I/II trial among 12 pediatric patients (SCOUT), and a phase II “basket” trial among 35 adult and adolescent patients (NAVIGATE).
“I want to emphasize that these patients were identified by local testing,” Dr. Hyman noted. “We did not perform central screening to find the TRK fusions, and in fact, 50 different laboratories identified the 55 patients. So this in a sense really represents the real-world identification of these patients.”
In an integrated analysis, the overall rate of confirmed response as assessed by investigators was 76%, with complete response in 12% of patients and partial response in 64%. Two patients had such deep tumor regression that they experienced downstaging enabling them to undergo potentially curative surgery. Efficacy was consistent regardless of tumor type, which TRK gene was affected, and the fusion partner gene.
Median time to response was 1.8 months. “This is actually just a reflection of when the first scan was obtained. But in the clinic, patients reported dramatic improvement of their symptoms within days of beginning therapy,” Dr. Hyman said.
With a median follow-up of 5.8 months, the median duration of response was not yet reached. Fully 79% of responses were still ongoing at 12 months. Median progression-free survival was likewise not reached; the 12-month rate was 63%.
The leading treatment-emergent adverse events were fatigue (38%), dizziness (27%), nausea (26%), and anemia (26%). “This is an extremely well tolerated therapy with only 13% of patients requiring any form of dose modification and not a single patient discontinuing due to adverse events,” he said.
It is unclear why some patients had apparent primary resistance to larotrectinib, but their TRK fusion test results may have been incorrect, Dr. Hyman speculated. Six patients developed acquired resistance to larotrectinib; five of them were found to have an identical resistance mutation, and two went on to receive and have a response to LOXO-195, a next-generation TRK inhibitor that appears to retain activity in the presence of this mutation (Cancer Discov. 2017 June 3. doi: 10.1158/2159-8290.CD-17-0507).
Dr. Hyman disclosed that he has a consulting or advisory role with Atara Biotherapeutics, Chugai Pharma, and CytomX Therapeutics, and that he receives research funding from AstraZeneca and Puma Biotechnology.
CHICAGO – Larotrectinib, an oral inhibitor of tropomyosin receptor kinase (TRK), has durable efficacy across diverse adult and pediatric cancers that harbor a genetic aberration known as TRK fusion, finds an analysis of three trials reported at the annual meeting of the American Society of Clinical Oncology.
Fusion of a TRK gene with an unrelated gene leads to uncontrolled signaling in the TRK pathway, potentially causing tumor growth and addiction to this input, lead author David Hyman, MD, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York explained in a press briefing.
Dr. Hyman and his colleagues analyzed data from 55 patients having 17 discrete types of advanced cancer harboring TRK fusions who were treated with larotrectinib in phase I and II trials. Results showed an overall response rate of 76%, and the large majority of responses were still ongoing at 12 months.
“I believe these data support larotrectinib as a potential new standard of care for these patients,” he said. “However, I want to emphasize that really recognizing this benefit in the community will require that we test patients more universally for the presence of TRK fusions or other tumor-agnostic biomarkers, such as microsatellite instability.”
On the basis of these promising data, the drug’s manufacturer, Loxo Oncology, plans to submit a New Drug Application to the Food and Drug Administration later this year or early next year. Larotrectinib has already been granted both orphan drug designation (for drugs used to treat rare conditions) and breakthrough therapy designation (for drugs used to treat serious conditions showing greater efficacy than available therapies).
A randomized trial pitting larotrectinib against other therapies is unlikely given the low prevalence of TRK fusions, the lack of treatment options for the fairly heavily pretreated trial patients, and the drug’s impressive performance, according to Dr. Hyman.
“The efficacy is so striking that it really exceeds almost any existing standard of care for solid tumors,” he elaborated. “There is hardly any chemotherapy or targeted therapy that has a response rate or durability that looks like larotrectinib in these patients.”
Expert perspective
The data for larotrectinib “really bring us into a new era where treatment is truly based on mutation, not location,” said Sumanta Kumar Pal, MD, a medical oncologist at City of Hope, in Duarte, Calif. “When I was in training, which was not too long ago, it really would have been a pipe dream to think that we could have treated cancers independent of their site of origin. … With the data presented by Dr. Hyman for larotrectinib, we may now be poised to treat many cancers in a manner that is agnostic of their site of origin and that is instead based on molecular criteria.
TRK testing
Several next-generation sequencing–based tests already available clinically can pick up TRK fusions, Dr. Hyman pointed out. “But it is important for the ordering physician to understand whether the tests they are ordering includes fusion detection and, if it’s an option, to select it. Otherwise, they will not find TRK fusions.
“The list price for these tests is in the kind of low thousands of dollars, which equates essentially to a PET scan for the cancer patient,” he noted. In cancers where sequential single-gene testing is already being done as standard of care, there is “minimal” incremental cost of instead using comprehensive testing that would detect TRK fusions.
Oncologists should be aware that obtaining test results can take weeks, Dr. Hyman stressed. “My personal opinion is that this [testing] should be more broadly adopted and should be adopted at a point in the patient’s treatment … [so that they] don’t become too sick, as we see in our own experience as well, and don’t have an opportunity to be treated even when the test results come back positive. So I would generally advocate early testing.”
Study details
For the study, which was funded by Loxo Oncology, the investigators analyzed data from three trials in which patients with advanced TRK fusion–positive solid cancers received larotrectinib (LOXO-101): a phase I trial among 8 adult patients, a phase I/II trial among 12 pediatric patients (SCOUT), and a phase II “basket” trial among 35 adult and adolescent patients (NAVIGATE).
“I want to emphasize that these patients were identified by local testing,” Dr. Hyman noted. “We did not perform central screening to find the TRK fusions, and in fact, 50 different laboratories identified the 55 patients. So this in a sense really represents the real-world identification of these patients.”
In an integrated analysis, the overall rate of confirmed response as assessed by investigators was 76%, with complete response in 12% of patients and partial response in 64%. Two patients had such deep tumor regression that they experienced downstaging enabling them to undergo potentially curative surgery. Efficacy was consistent regardless of tumor type, which TRK gene was affected, and the fusion partner gene.
Median time to response was 1.8 months. “This is actually just a reflection of when the first scan was obtained. But in the clinic, patients reported dramatic improvement of their symptoms within days of beginning therapy,” Dr. Hyman said.
With a median follow-up of 5.8 months, the median duration of response was not yet reached. Fully 79% of responses were still ongoing at 12 months. Median progression-free survival was likewise not reached; the 12-month rate was 63%.
The leading treatment-emergent adverse events were fatigue (38%), dizziness (27%), nausea (26%), and anemia (26%). “This is an extremely well tolerated therapy with only 13% of patients requiring any form of dose modification and not a single patient discontinuing due to adverse events,” he said.
It is unclear why some patients had apparent primary resistance to larotrectinib, but their TRK fusion test results may have been incorrect, Dr. Hyman speculated. Six patients developed acquired resistance to larotrectinib; five of them were found to have an identical resistance mutation, and two went on to receive and have a response to LOXO-195, a next-generation TRK inhibitor that appears to retain activity in the presence of this mutation (Cancer Discov. 2017 June 3. doi: 10.1158/2159-8290.CD-17-0507).
Dr. Hyman disclosed that he has a consulting or advisory role with Atara Biotherapeutics, Chugai Pharma, and CytomX Therapeutics, and that he receives research funding from AstraZeneca and Puma Biotechnology.
CHICAGO – Larotrectinib, an oral inhibitor of tropomyosin receptor kinase (TRK), has durable efficacy across diverse adult and pediatric cancers that harbor a genetic aberration known as TRK fusion, finds an analysis of three trials reported at the annual meeting of the American Society of Clinical Oncology.
Fusion of a TRK gene with an unrelated gene leads to uncontrolled signaling in the TRK pathway, potentially causing tumor growth and addiction to this input, lead author David Hyman, MD, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York explained in a press briefing.
Dr. Hyman and his colleagues analyzed data from 55 patients having 17 discrete types of advanced cancer harboring TRK fusions who were treated with larotrectinib in phase I and II trials. Results showed an overall response rate of 76%, and the large majority of responses were still ongoing at 12 months.
“I believe these data support larotrectinib as a potential new standard of care for these patients,” he said. “However, I want to emphasize that really recognizing this benefit in the community will require that we test patients more universally for the presence of TRK fusions or other tumor-agnostic biomarkers, such as microsatellite instability.”
On the basis of these promising data, the drug’s manufacturer, Loxo Oncology, plans to submit a New Drug Application to the Food and Drug Administration later this year or early next year. Larotrectinib has already been granted both orphan drug designation (for drugs used to treat rare conditions) and breakthrough therapy designation (for drugs used to treat serious conditions showing greater efficacy than available therapies).
A randomized trial pitting larotrectinib against other therapies is unlikely given the low prevalence of TRK fusions, the lack of treatment options for the fairly heavily pretreated trial patients, and the drug’s impressive performance, according to Dr. Hyman.
“The efficacy is so striking that it really exceeds almost any existing standard of care for solid tumors,” he elaborated. “There is hardly any chemotherapy or targeted therapy that has a response rate or durability that looks like larotrectinib in these patients.”
Expert perspective
The data for larotrectinib “really bring us into a new era where treatment is truly based on mutation, not location,” said Sumanta Kumar Pal, MD, a medical oncologist at City of Hope, in Duarte, Calif. “When I was in training, which was not too long ago, it really would have been a pipe dream to think that we could have treated cancers independent of their site of origin. … With the data presented by Dr. Hyman for larotrectinib, we may now be poised to treat many cancers in a manner that is agnostic of their site of origin and that is instead based on molecular criteria.
TRK testing
Several next-generation sequencing–based tests already available clinically can pick up TRK fusions, Dr. Hyman pointed out. “But it is important for the ordering physician to understand whether the tests they are ordering includes fusion detection and, if it’s an option, to select it. Otherwise, they will not find TRK fusions.
“The list price for these tests is in the kind of low thousands of dollars, which equates essentially to a PET scan for the cancer patient,” he noted. In cancers where sequential single-gene testing is already being done as standard of care, there is “minimal” incremental cost of instead using comprehensive testing that would detect TRK fusions.
Oncologists should be aware that obtaining test results can take weeks, Dr. Hyman stressed. “My personal opinion is that this [testing] should be more broadly adopted and should be adopted at a point in the patient’s treatment … [so that they] don’t become too sick, as we see in our own experience as well, and don’t have an opportunity to be treated even when the test results come back positive. So I would generally advocate early testing.”
Study details
For the study, which was funded by Loxo Oncology, the investigators analyzed data from three trials in which patients with advanced TRK fusion–positive solid cancers received larotrectinib (LOXO-101): a phase I trial among 8 adult patients, a phase I/II trial among 12 pediatric patients (SCOUT), and a phase II “basket” trial among 35 adult and adolescent patients (NAVIGATE).
“I want to emphasize that these patients were identified by local testing,” Dr. Hyman noted. “We did not perform central screening to find the TRK fusions, and in fact, 50 different laboratories identified the 55 patients. So this in a sense really represents the real-world identification of these patients.”
In an integrated analysis, the overall rate of confirmed response as assessed by investigators was 76%, with complete response in 12% of patients and partial response in 64%. Two patients had such deep tumor regression that they experienced downstaging enabling them to undergo potentially curative surgery. Efficacy was consistent regardless of tumor type, which TRK gene was affected, and the fusion partner gene.
Median time to response was 1.8 months. “This is actually just a reflection of when the first scan was obtained. But in the clinic, patients reported dramatic improvement of their symptoms within days of beginning therapy,” Dr. Hyman said.
With a median follow-up of 5.8 months, the median duration of response was not yet reached. Fully 79% of responses were still ongoing at 12 months. Median progression-free survival was likewise not reached; the 12-month rate was 63%.
The leading treatment-emergent adverse events were fatigue (38%), dizziness (27%), nausea (26%), and anemia (26%). “This is an extremely well tolerated therapy with only 13% of patients requiring any form of dose modification and not a single patient discontinuing due to adverse events,” he said.
It is unclear why some patients had apparent primary resistance to larotrectinib, but their TRK fusion test results may have been incorrect, Dr. Hyman speculated. Six patients developed acquired resistance to larotrectinib; five of them were found to have an identical resistance mutation, and two went on to receive and have a response to LOXO-195, a next-generation TRK inhibitor that appears to retain activity in the presence of this mutation (Cancer Discov. 2017 June 3. doi: 10.1158/2159-8290.CD-17-0507).
Dr. Hyman disclosed that he has a consulting or advisory role with Atara Biotherapeutics, Chugai Pharma, and CytomX Therapeutics, and that he receives research funding from AstraZeneca and Puma Biotechnology.
AT ASCO 2017
Key clinical point:
Major finding: The overall response rate was 76%, and 79% of responses were still ongoing at 12 months.
Data source: An integrated analysis of phase I and II trials among 55 children and adults having 17 discrete types of advanced cancer with TRK fusions.
Disclosures: Dr. Hyman disclosed that he has a consulting or advisory role with Atara Biotherapeutics, Chugai Pharma, and CytomX Therapeutics, and that he receives research funding from AstraZeneca and Puma Biotechnology. The study was funded by Loxo Oncology.
VIDEO: Survival improves when cancer patients self-report symptoms
CHICAGO – Patients with metastatic cancer who self-reported symptoms during routine cancer treatment experienced a number of benefits, including a statistically significant improvement in overall survival, according to findings from a randomized, controlled clinical trial.
The median overall survival among 441 patients receiving treatment for metastatic breast, lung, genitourinary, or gynecologic cancer who were randomized to the intervention arm was more than 5 months longer – a nearly 20% increase – than in 325 patients who received standard care (31.2 vs. 26 months), Ethan Basch, MD, reported at the annual meeting of the American Society of Clinical Oncology.
Additionally, 31% of patients in the intervention arm had better quality of life/physical functioning, compared with those in the control arm, and 7% fewer patients in the intervention arm visited an emergency room during the course of the study. The duration of potentially life-prolonging chemotherapy was increased by an average of 2 months in the intervention arm, he said.
The findings were simultaneously published online in a research letter in JAMA (2017 Jun 4. doi: 10.1001/jama.2017.7156).
Symptoms such as nausea, pain, and fatigue are common among patients with metastatic cancer, Dr. Basch said. “Unfortunately, they often go undetected by doctors and nurses until they become severe and physically debilitating,” he added, explaining that patients are often hesitant to call the office to report symptoms between visits.
Even at office visits, competing topics can interfere with communication about symptoms, he noted.
He and his colleagues hypothesized that self-reporting of patient symptoms between visits or prior to a visit while in the clinic waiting area would prompt earlier intervention and improve symptom control and outcomes.
Study subjects were patients at Memorial Sloan Kettering Cancer Center who had advanced solid genitourinary, gynecologic, breast, or lung tumors and who were receiving outpatient chemotherapy. Those assigned to the intervention group used tablet computers and an online web survey system to report on 12 symptoms commonly experienced during chemotherapy. The system triggers an alert to a nurse when a severe or worsening symptom is reported. Patients in the usual care group discussed symptoms during office visits and were encouraged to call the office between visits if they experienced concerning symptoms.
Patients remained on the study until discontinuation of all cancer treatment, hospice, or death.
One possible explanation for the findings is that this self-reporting approach prompts clinicians to manage symptoms before they cause serious downstream complications, Dr. Basch said.
The approach may also keep patients more physically functional, which is known from prior studies to have a strong association with better survival, and the approach may also improve management of chemotherapy side effects, enabling longer duration of beneficial cancer treatment, he said, explaining that, “in oncology, we often are limited in our ability to give life-prolonging treatment because people don’t tolerate it well.”
“This approach should be considered for inclusion in standard symptoms management as a component of high quality cancer care,” he concluded, noting that efforts are underway to test the next generation of systems to improve communication between patients and care teams and to figure out how best to integrate these tools into oncology practice.
The system used in the this study was designed for research, but a number of companies have tools currently available for patient-reported outcomes, and others are being developed, Dr. Basch said, noting that a National Cancer Institute questionnaire – the PRO-CTCAE – is publicly available and could be loaded into patients’ electronic health records for this purpose as well.
ASCO’s chief medical officer, Richard L. Schilsky, MD, said the findings demonstrate that “these frequent touches between the patient and their health care providers obviously can make a huge difference in their outcomes.”
Additionally, ASCO expert Harold J. Burstein, MD, of Dana-Farber Cancer Institute, Boston, said this “exciting and compelling study” validates the feeling among many clinicians that patient-focused, team-based care can improve outcomes in a meaningful way for patients. In a video interview, he further discusses the challenges with implementing a system like this and particularly with obtaining funding to support implementation.
“If this was a drug, if it was iPad-olizumab, it would be worth tens, if not hundreds of thousands, of dollars per year to have something that improved overall survival. We don’t have those same kinds of dollars to help implement these into our electronic health records or our systems. We need to find ways to support that and make it happen,” he said.
This study was supported by the National Institutes of Health and the Conquer Cancer Foundation of the American Society of Clinical Oncology. Dr. Basch and Dr. Burstein each reported having no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Patients with metastatic cancer who self-reported symptoms during routine cancer treatment experienced a number of benefits, including a statistically significant improvement in overall survival, according to findings from a randomized, controlled clinical trial.
The median overall survival among 441 patients receiving treatment for metastatic breast, lung, genitourinary, or gynecologic cancer who were randomized to the intervention arm was more than 5 months longer – a nearly 20% increase – than in 325 patients who received standard care (31.2 vs. 26 months), Ethan Basch, MD, reported at the annual meeting of the American Society of Clinical Oncology.
Additionally, 31% of patients in the intervention arm had better quality of life/physical functioning, compared with those in the control arm, and 7% fewer patients in the intervention arm visited an emergency room during the course of the study. The duration of potentially life-prolonging chemotherapy was increased by an average of 2 months in the intervention arm, he said.
The findings were simultaneously published online in a research letter in JAMA (2017 Jun 4. doi: 10.1001/jama.2017.7156).
Symptoms such as nausea, pain, and fatigue are common among patients with metastatic cancer, Dr. Basch said. “Unfortunately, they often go undetected by doctors and nurses until they become severe and physically debilitating,” he added, explaining that patients are often hesitant to call the office to report symptoms between visits.
Even at office visits, competing topics can interfere with communication about symptoms, he noted.
He and his colleagues hypothesized that self-reporting of patient symptoms between visits or prior to a visit while in the clinic waiting area would prompt earlier intervention and improve symptom control and outcomes.
Study subjects were patients at Memorial Sloan Kettering Cancer Center who had advanced solid genitourinary, gynecologic, breast, or lung tumors and who were receiving outpatient chemotherapy. Those assigned to the intervention group used tablet computers and an online web survey system to report on 12 symptoms commonly experienced during chemotherapy. The system triggers an alert to a nurse when a severe or worsening symptom is reported. Patients in the usual care group discussed symptoms during office visits and were encouraged to call the office between visits if they experienced concerning symptoms.
Patients remained on the study until discontinuation of all cancer treatment, hospice, or death.
One possible explanation for the findings is that this self-reporting approach prompts clinicians to manage symptoms before they cause serious downstream complications, Dr. Basch said.
The approach may also keep patients more physically functional, which is known from prior studies to have a strong association with better survival, and the approach may also improve management of chemotherapy side effects, enabling longer duration of beneficial cancer treatment, he said, explaining that, “in oncology, we often are limited in our ability to give life-prolonging treatment because people don’t tolerate it well.”
“This approach should be considered for inclusion in standard symptoms management as a component of high quality cancer care,” he concluded, noting that efforts are underway to test the next generation of systems to improve communication between patients and care teams and to figure out how best to integrate these tools into oncology practice.
The system used in the this study was designed for research, but a number of companies have tools currently available for patient-reported outcomes, and others are being developed, Dr. Basch said, noting that a National Cancer Institute questionnaire – the PRO-CTCAE – is publicly available and could be loaded into patients’ electronic health records for this purpose as well.
ASCO’s chief medical officer, Richard L. Schilsky, MD, said the findings demonstrate that “these frequent touches between the patient and their health care providers obviously can make a huge difference in their outcomes.”
Additionally, ASCO expert Harold J. Burstein, MD, of Dana-Farber Cancer Institute, Boston, said this “exciting and compelling study” validates the feeling among many clinicians that patient-focused, team-based care can improve outcomes in a meaningful way for patients. In a video interview, he further discusses the challenges with implementing a system like this and particularly with obtaining funding to support implementation.
“If this was a drug, if it was iPad-olizumab, it would be worth tens, if not hundreds of thousands, of dollars per year to have something that improved overall survival. We don’t have those same kinds of dollars to help implement these into our electronic health records or our systems. We need to find ways to support that and make it happen,” he said.
This study was supported by the National Institutes of Health and the Conquer Cancer Foundation of the American Society of Clinical Oncology. Dr. Basch and Dr. Burstein each reported having no disclosures.
CHICAGO – Patients with metastatic cancer who self-reported symptoms during routine cancer treatment experienced a number of benefits, including a statistically significant improvement in overall survival, according to findings from a randomized, controlled clinical trial.
The median overall survival among 441 patients receiving treatment for metastatic breast, lung, genitourinary, or gynecologic cancer who were randomized to the intervention arm was more than 5 months longer – a nearly 20% increase – than in 325 patients who received standard care (31.2 vs. 26 months), Ethan Basch, MD, reported at the annual meeting of the American Society of Clinical Oncology.
Additionally, 31% of patients in the intervention arm had better quality of life/physical functioning, compared with those in the control arm, and 7% fewer patients in the intervention arm visited an emergency room during the course of the study. The duration of potentially life-prolonging chemotherapy was increased by an average of 2 months in the intervention arm, he said.
The findings were simultaneously published online in a research letter in JAMA (2017 Jun 4. doi: 10.1001/jama.2017.7156).
Symptoms such as nausea, pain, and fatigue are common among patients with metastatic cancer, Dr. Basch said. “Unfortunately, they often go undetected by doctors and nurses until they become severe and physically debilitating,” he added, explaining that patients are often hesitant to call the office to report symptoms between visits.
Even at office visits, competing topics can interfere with communication about symptoms, he noted.
He and his colleagues hypothesized that self-reporting of patient symptoms between visits or prior to a visit while in the clinic waiting area would prompt earlier intervention and improve symptom control and outcomes.
Study subjects were patients at Memorial Sloan Kettering Cancer Center who had advanced solid genitourinary, gynecologic, breast, or lung tumors and who were receiving outpatient chemotherapy. Those assigned to the intervention group used tablet computers and an online web survey system to report on 12 symptoms commonly experienced during chemotherapy. The system triggers an alert to a nurse when a severe or worsening symptom is reported. Patients in the usual care group discussed symptoms during office visits and were encouraged to call the office between visits if they experienced concerning symptoms.
Patients remained on the study until discontinuation of all cancer treatment, hospice, or death.
One possible explanation for the findings is that this self-reporting approach prompts clinicians to manage symptoms before they cause serious downstream complications, Dr. Basch said.
The approach may also keep patients more physically functional, which is known from prior studies to have a strong association with better survival, and the approach may also improve management of chemotherapy side effects, enabling longer duration of beneficial cancer treatment, he said, explaining that, “in oncology, we often are limited in our ability to give life-prolonging treatment because people don’t tolerate it well.”
“This approach should be considered for inclusion in standard symptoms management as a component of high quality cancer care,” he concluded, noting that efforts are underway to test the next generation of systems to improve communication between patients and care teams and to figure out how best to integrate these tools into oncology practice.
The system used in the this study was designed for research, but a number of companies have tools currently available for patient-reported outcomes, and others are being developed, Dr. Basch said, noting that a National Cancer Institute questionnaire – the PRO-CTCAE – is publicly available and could be loaded into patients’ electronic health records for this purpose as well.
ASCO’s chief medical officer, Richard L. Schilsky, MD, said the findings demonstrate that “these frequent touches between the patient and their health care providers obviously can make a huge difference in their outcomes.”
Additionally, ASCO expert Harold J. Burstein, MD, of Dana-Farber Cancer Institute, Boston, said this “exciting and compelling study” validates the feeling among many clinicians that patient-focused, team-based care can improve outcomes in a meaningful way for patients. In a video interview, he further discusses the challenges with implementing a system like this and particularly with obtaining funding to support implementation.
“If this was a drug, if it was iPad-olizumab, it would be worth tens, if not hundreds of thousands, of dollars per year to have something that improved overall survival. We don’t have those same kinds of dollars to help implement these into our electronic health records or our systems. We need to find ways to support that and make it happen,” he said.
This study was supported by the National Institutes of Health and the Conquer Cancer Foundation of the American Society of Clinical Oncology. Dr. Basch and Dr. Burstein each reported having no disclosures.
AT THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: Median overall survival was 31.2, vs. 26 months, with self-reporting of symptoms, vs. usual care.
Data source: A randomized controlled clinical trial of 766 patients.
Disclosures: This study was supported by the National Institutes of Health and the Conquer Cancer Foundation of the American Society of Clinical Oncology. Dr. Basch and Dr. Burstein each reported having no disclosures.
Immune-agonist combo has activity against several tumor types
CHICAGO – A combination of the programmed death 1 (PD-1) inhibitor nivolumab (Opdivo) with an experimental immune-enhancing monoclonal antibody induced clinical responses in patients with several different solid tumor types, including some patients who had disease progression on a PD-1 inhibitor, investigators reported.
The investigational agent, euphoniously named BMS-986156 (986156), is a fully human immunoglobulin G1 agonist monoclonal antibody with high affinity binding for the glucocorticoid-induced tumor necrosis factor receptor–related gene (GITR).
BMS-986156156 “induces potent antitumor immunity by several mechanisms. First, it increases T-effector cell survival and function. Second, it promotes T-regulatory cell depletion and reduction through its conversion to other immune cells. As well, it reduces T-reg-mediated suppression of T-effector cells,” said Lillian L Siu, MD, from the Princess Margaret Hospital in Toronto.
In preclinical studies, the combination of an anti-GITR and an anti-PD-1 agent showed synergistic activity against murine tumor models.
Dr. Siu and colleagues conducted a phase I/IIa study of BMS-986156 with or without nivolumab in 66 patients with advanced solid tumors.
The 29 patients assigned to BMS-986156 monotherapy were started at 10 mg every 2 weeks, which was gradually titrated upward to find the maximum tolerated dose of 240 mg Q2 weeks.
The 37 patients assigned to the combination were started on a dose of 30-mg nivolumab and 240-mg BMS-986156. The nivolumab dose but not the BMS-986156 dose was then titrated upward to a maximum tolerated dose of 240 mg for each agent. This dose was based on pharmacodynamic and pharmacokinetic studies.
Tumor types included melanoma, cervical, colon, breast, renal, pancreatic, and ovarian cancers and cholangiocarcinoma.
Approximately one-third of patients in the monotherapy arm and nearly half of those in the combination arm had undergone three or more prior therapies for cancer. Seven patients in the monotherapy group and five in the combination group had previously received a PD-1 or PD-L1 inhibitor.
The median duration of treatment ranged from 7 to 15.5 weeks for 156 monotherapy and 8 to 18 weeks for the combination.
Safe and well tolerated
There were no dose-limiting toxicities or treatment-related deaths in either study arm, and patients tolerated both BMS-986156 monotherapy and the combination well. There were no grade 3 or 4 adverse events in the monotherapy arm.
“In the combination arm, the toxicity is very consistent with that observed with nivolumab monotherapy alone,” Dr. Siu said.
The only grade 4 event in this group was an increase in blood creatine phosphokinase. In this group, there were six grade 3 adverse events, including one each of colitis, dehydration, fatigue and increases in hepatic enzymes, lipase increase, and lung infection.
In pharmacokinetic studies, the action of the combinations was linear, with dose-related increases in exposure, and the combination had low immunogenicity, with no patients developing persistent antidrug antibodies.
The combination was also associated with increases in natural killer and CD8 cells in peripheral blood. Immunophenotyping of patients treated with the 240/240-mg dose of the combination showed increased proliferation and activation of CD8 effector cells, central memory cells, and CD4 cells.
Early promise
Dr. Siu reviewed interim efficacy results for the five patients treated with the combination who had responses.
For example, a 44-year-old woman with metastatic cervical cancer – a tumor type known to have high levels of GITR expression – had received more than three prior lines of therapy, including chemotherapy with a vascular endothelial growth factor inhibitor. She had a partial response with the combination, with an approximately 62% reduction in tumor burden. She had an ongoing response to the combination at the time of data cutoff in March 2017.
Two other patients had partial responses after progression on an anti-PD-1 agents, including one with nasopharyngeal cancer who had received three prior lines of therapy, including chemotherapy and a PD-1 inhibitor. This patient had an approximately 43% reduction in tumor burden, with a 17-week duration of response and ongoing response at data cutoff.
The other patient was a 59-year-old with malignant melanoma that had advanced on pembrolizumab (Keytruda). This patient too had received three prior lines of therapy, including a BRAF inhibitor, anti-PD-1, and BRAF/MEK inhibitor combination.
This patient had a response of 24-week duration at the time of data cutoff. It is ongoing, Dr. Liu said.
“This combination of immune agonists was safe with a low incidence of severe toxicity, and there was no maximum tolerated dose; however, the maximum administered dose may not be the most effective dose to move forward,” commented Siwen Hu-Lieskovan MD, PhD, from the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, the invited discussant.
She noted that activity of the combination has been seen in a wide range of tumor histologies but added that further biomarker studies will be critical for identifying patients who are likely to respond.
The study was funded by Bristol-Myers Squibb. Dr. Siu disclosed research funding from the company and others and consulting/advising several different companies. Dr. Hu-Lieskovan disclosed institutional research funding from BMS and other companies, as well as honoraria and consulting and serving in an advisory capacity for companies other than BMS. Several coauthors are employees of the company.
CHICAGO – A combination of the programmed death 1 (PD-1) inhibitor nivolumab (Opdivo) with an experimental immune-enhancing monoclonal antibody induced clinical responses in patients with several different solid tumor types, including some patients who had disease progression on a PD-1 inhibitor, investigators reported.
The investigational agent, euphoniously named BMS-986156 (986156), is a fully human immunoglobulin G1 agonist monoclonal antibody with high affinity binding for the glucocorticoid-induced tumor necrosis factor receptor–related gene (GITR).
BMS-986156156 “induces potent antitumor immunity by several mechanisms. First, it increases T-effector cell survival and function. Second, it promotes T-regulatory cell depletion and reduction through its conversion to other immune cells. As well, it reduces T-reg-mediated suppression of T-effector cells,” said Lillian L Siu, MD, from the Princess Margaret Hospital in Toronto.
In preclinical studies, the combination of an anti-GITR and an anti-PD-1 agent showed synergistic activity against murine tumor models.
Dr. Siu and colleagues conducted a phase I/IIa study of BMS-986156 with or without nivolumab in 66 patients with advanced solid tumors.
The 29 patients assigned to BMS-986156 monotherapy were started at 10 mg every 2 weeks, which was gradually titrated upward to find the maximum tolerated dose of 240 mg Q2 weeks.
The 37 patients assigned to the combination were started on a dose of 30-mg nivolumab and 240-mg BMS-986156. The nivolumab dose but not the BMS-986156 dose was then titrated upward to a maximum tolerated dose of 240 mg for each agent. This dose was based on pharmacodynamic and pharmacokinetic studies.
Tumor types included melanoma, cervical, colon, breast, renal, pancreatic, and ovarian cancers and cholangiocarcinoma.
Approximately one-third of patients in the monotherapy arm and nearly half of those in the combination arm had undergone three or more prior therapies for cancer. Seven patients in the monotherapy group and five in the combination group had previously received a PD-1 or PD-L1 inhibitor.
The median duration of treatment ranged from 7 to 15.5 weeks for 156 monotherapy and 8 to 18 weeks for the combination.
Safe and well tolerated
There were no dose-limiting toxicities or treatment-related deaths in either study arm, and patients tolerated both BMS-986156 monotherapy and the combination well. There were no grade 3 or 4 adverse events in the monotherapy arm.
“In the combination arm, the toxicity is very consistent with that observed with nivolumab monotherapy alone,” Dr. Siu said.
The only grade 4 event in this group was an increase in blood creatine phosphokinase. In this group, there were six grade 3 adverse events, including one each of colitis, dehydration, fatigue and increases in hepatic enzymes, lipase increase, and lung infection.
In pharmacokinetic studies, the action of the combinations was linear, with dose-related increases in exposure, and the combination had low immunogenicity, with no patients developing persistent antidrug antibodies.
The combination was also associated with increases in natural killer and CD8 cells in peripheral blood. Immunophenotyping of patients treated with the 240/240-mg dose of the combination showed increased proliferation and activation of CD8 effector cells, central memory cells, and CD4 cells.
Early promise
Dr. Siu reviewed interim efficacy results for the five patients treated with the combination who had responses.
For example, a 44-year-old woman with metastatic cervical cancer – a tumor type known to have high levels of GITR expression – had received more than three prior lines of therapy, including chemotherapy with a vascular endothelial growth factor inhibitor. She had a partial response with the combination, with an approximately 62% reduction in tumor burden. She had an ongoing response to the combination at the time of data cutoff in March 2017.
Two other patients had partial responses after progression on an anti-PD-1 agents, including one with nasopharyngeal cancer who had received three prior lines of therapy, including chemotherapy and a PD-1 inhibitor. This patient had an approximately 43% reduction in tumor burden, with a 17-week duration of response and ongoing response at data cutoff.
The other patient was a 59-year-old with malignant melanoma that had advanced on pembrolizumab (Keytruda). This patient too had received three prior lines of therapy, including a BRAF inhibitor, anti-PD-1, and BRAF/MEK inhibitor combination.
This patient had a response of 24-week duration at the time of data cutoff. It is ongoing, Dr. Liu said.
“This combination of immune agonists was safe with a low incidence of severe toxicity, and there was no maximum tolerated dose; however, the maximum administered dose may not be the most effective dose to move forward,” commented Siwen Hu-Lieskovan MD, PhD, from the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, the invited discussant.
She noted that activity of the combination has been seen in a wide range of tumor histologies but added that further biomarker studies will be critical for identifying patients who are likely to respond.
The study was funded by Bristol-Myers Squibb. Dr. Siu disclosed research funding from the company and others and consulting/advising several different companies. Dr. Hu-Lieskovan disclosed institutional research funding from BMS and other companies, as well as honoraria and consulting and serving in an advisory capacity for companies other than BMS. Several coauthors are employees of the company.
CHICAGO – A combination of the programmed death 1 (PD-1) inhibitor nivolumab (Opdivo) with an experimental immune-enhancing monoclonal antibody induced clinical responses in patients with several different solid tumor types, including some patients who had disease progression on a PD-1 inhibitor, investigators reported.
The investigational agent, euphoniously named BMS-986156 (986156), is a fully human immunoglobulin G1 agonist monoclonal antibody with high affinity binding for the glucocorticoid-induced tumor necrosis factor receptor–related gene (GITR).
BMS-986156156 “induces potent antitumor immunity by several mechanisms. First, it increases T-effector cell survival and function. Second, it promotes T-regulatory cell depletion and reduction through its conversion to other immune cells. As well, it reduces T-reg-mediated suppression of T-effector cells,” said Lillian L Siu, MD, from the Princess Margaret Hospital in Toronto.
In preclinical studies, the combination of an anti-GITR and an anti-PD-1 agent showed synergistic activity against murine tumor models.
Dr. Siu and colleagues conducted a phase I/IIa study of BMS-986156 with or without nivolumab in 66 patients with advanced solid tumors.
The 29 patients assigned to BMS-986156 monotherapy were started at 10 mg every 2 weeks, which was gradually titrated upward to find the maximum tolerated dose of 240 mg Q2 weeks.
The 37 patients assigned to the combination were started on a dose of 30-mg nivolumab and 240-mg BMS-986156. The nivolumab dose but not the BMS-986156 dose was then titrated upward to a maximum tolerated dose of 240 mg for each agent. This dose was based on pharmacodynamic and pharmacokinetic studies.
Tumor types included melanoma, cervical, colon, breast, renal, pancreatic, and ovarian cancers and cholangiocarcinoma.
Approximately one-third of patients in the monotherapy arm and nearly half of those in the combination arm had undergone three or more prior therapies for cancer. Seven patients in the monotherapy group and five in the combination group had previously received a PD-1 or PD-L1 inhibitor.
The median duration of treatment ranged from 7 to 15.5 weeks for 156 monotherapy and 8 to 18 weeks for the combination.
Safe and well tolerated
There were no dose-limiting toxicities or treatment-related deaths in either study arm, and patients tolerated both BMS-986156 monotherapy and the combination well. There were no grade 3 or 4 adverse events in the monotherapy arm.
“In the combination arm, the toxicity is very consistent with that observed with nivolumab monotherapy alone,” Dr. Siu said.
The only grade 4 event in this group was an increase in blood creatine phosphokinase. In this group, there were six grade 3 adverse events, including one each of colitis, dehydration, fatigue and increases in hepatic enzymes, lipase increase, and lung infection.
In pharmacokinetic studies, the action of the combinations was linear, with dose-related increases in exposure, and the combination had low immunogenicity, with no patients developing persistent antidrug antibodies.
The combination was also associated with increases in natural killer and CD8 cells in peripheral blood. Immunophenotyping of patients treated with the 240/240-mg dose of the combination showed increased proliferation and activation of CD8 effector cells, central memory cells, and CD4 cells.
Early promise
Dr. Siu reviewed interim efficacy results for the five patients treated with the combination who had responses.
For example, a 44-year-old woman with metastatic cervical cancer – a tumor type known to have high levels of GITR expression – had received more than three prior lines of therapy, including chemotherapy with a vascular endothelial growth factor inhibitor. She had a partial response with the combination, with an approximately 62% reduction in tumor burden. She had an ongoing response to the combination at the time of data cutoff in March 2017.
Two other patients had partial responses after progression on an anti-PD-1 agents, including one with nasopharyngeal cancer who had received three prior lines of therapy, including chemotherapy and a PD-1 inhibitor. This patient had an approximately 43% reduction in tumor burden, with a 17-week duration of response and ongoing response at data cutoff.
The other patient was a 59-year-old with malignant melanoma that had advanced on pembrolizumab (Keytruda). This patient too had received three prior lines of therapy, including a BRAF inhibitor, anti-PD-1, and BRAF/MEK inhibitor combination.
This patient had a response of 24-week duration at the time of data cutoff. It is ongoing, Dr. Liu said.
“This combination of immune agonists was safe with a low incidence of severe toxicity, and there was no maximum tolerated dose; however, the maximum administered dose may not be the most effective dose to move forward,” commented Siwen Hu-Lieskovan MD, PhD, from the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, the invited discussant.
She noted that activity of the combination has been seen in a wide range of tumor histologies but added that further biomarker studies will be critical for identifying patients who are likely to respond.
The study was funded by Bristol-Myers Squibb. Dr. Siu disclosed research funding from the company and others and consulting/advising several different companies. Dr. Hu-Lieskovan disclosed institutional research funding from BMS and other companies, as well as honoraria and consulting and serving in an advisory capacity for companies other than BMS. Several coauthors are employees of the company.
AT ASCO 2017
Key clinical point: A combination of a GITR-agonist and anti-PD-1 agent was safe and produced partial responses in patients with heavily pretreated advanced cancers.
Major finding: Two patients with cancers that had progression on a PD-1 inhibitor had durable partial responses.
Data source: A phase I/IIa dose-finding and safety study of BMS986156 alone or in combination with nivolumab (Opdivo).
Disclosures: The study was funded by Bristol-Myers Squibb. Dr. Siu disclosed research funding from the company and others and consulting/advising for several different companies. Dr. Hu-Lieskovan disclosed institutional research funding from BMS and other companies, as well as honoraria and consulting and serving in an advisory capacity for companies other than BMS. Several coauthors are employees of the company.
CAR T cells elicit durable, potent responses in kids with EM relapse of ALL
CHICAGO—Outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) are dismal, with the probability of event-free survival ranging from 15% to 70% after a first relapse to 15% to 20% after a second relapse.
“So novel therapies are obviously urgently needed,” Mala Kiran Talekar, MD, of the Children's Hospital of Philadelphia in Pennsylvania, affirmed. “And herein comes the role of CAR T cells as a breakthrough therapy for relapsed/refractory pediatric ALL.”
She presented the outcome of chimeric antigen receptor (CAR) T-cell therapy in pediatric patients with non-CNS extramedullary (EM) relapse at the ASCO 2017 Annual meeting as abstract 10507.
The investigators had drawn the patient population for this analysis from 2 CAR studies, CTL019 and CTL119.
CTL019, which had already been completed, employed a murine CAR, and CTL119 is ongoing and uses a humanized CAR.
Of the 60 patients enrolled in CTL019, 56 (93%) achieved a complete response (CR) at day 28, and 100% had a CNS remission. Their 12-month overall survival (OS) was 79%.
“[K]eep in mind, when the study first started,” Dr Talekar said, “the patient population that had been referred to us was patients who had suffered a second or greater relapse or had been refractory to forms of treatment available to them, and the majority had been refractory to multiple therapies.”
The humanized CAR study, CTL119, is divided into 2 cohorts—one with CAR-naïve patients (n=22) and the other a CAR-retreatment arm (n=15) with patients who had received previous CAR therapy and relapsed.
Dr Talekar explained that the humanized CAR was made with the intention of decreasing rejection or loss of persistence of the T cells related to murine antigenicity.
Nine patients (60%) in the CAR-retreatment arm achieved a CR at day 28, and at 6 months, 78% experienced relapse-free survival (RFS) with a median follow-up of 12 months.
All of the CAR-naïve patients achieved CR at day 28, with 86% achieving RFS at 6 months, with a median follow-up of 10 months.
ALL with EM involvement
The investigators identified 10 pediatric patients treated in the murine (n=6) or humanized (n=4) trials who had received CAR therapy for isolated extramedullary disease or for combined bone marrow extramedullary (BM/EM) relapse of ALL.
They defined EM relapse as involvement of a non-CNS site confirmed by imaging with or without pathology within 12 months of CAR T-cell infusion. After infusion, patients had diagnostic imaging performed at 1, 3, 6, 9, and 12 months.
Of the 10 patients, 5 had active EM involvement at the time of infusion, 2 had isolated EM relapse—1 with parotid and multifocal bony lesions and 1 with testis and sinus lesions—and 5 had multiple sites of EM relapse.
The patients had 2 to 4 prior ALL relapses, 2 had prior local radiation to the EM site, and all 10 had received prior bone marrow transplants.
Three patients had an MLL rearrangement, 1 had hypodiploid ALL, and 1 had trisomy 21.
Nine of the 10 patients achieved MRD-negative CR at day 28.
One patient was not evaluable because his disease progressed within 2 weeks of CAR therapy in both the bone marrow and EM site. He died 6 weeks after the infusion.
Five patients evaluated by serial imaging had objective responses. Two had no evidence of EM disease by day 28, 2 had resolution by 3 months, and 1 had continued decrease in the size of her uterine mass at 3 and 6 months. She underwent hysterectomy at 8 months with no evidence of disease on pathology.
Four patients with a prior history of skin or testicular involvement had no evidence of disease by exam at day 28.
Three of the 9 patients relapsed with CD19+ disease. One had skin/medullary involvement and died at 38 months after CAR T-cell infusion. And 2 had medullary disease: 1 died at 17 months and 1 is alive at 28 months.
The remaining 6 patients are alive and well at a median follow-up of 10 months (range, 3 – 16 months) without recurrence of disease.
The investigators therefore concluded that single agent CAR T-cell immunotherapy can induce potent and durable response in patients with EM relapse of their ALL. 
CHICAGO—Outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) are dismal, with the probability of event-free survival ranging from 15% to 70% after a first relapse to 15% to 20% after a second relapse.
“So novel therapies are obviously urgently needed,” Mala Kiran Talekar, MD, of the Children's Hospital of Philadelphia in Pennsylvania, affirmed. “And herein comes the role of CAR T cells as a breakthrough therapy for relapsed/refractory pediatric ALL.”
She presented the outcome of chimeric antigen receptor (CAR) T-cell therapy in pediatric patients with non-CNS extramedullary (EM) relapse at the ASCO 2017 Annual meeting as abstract 10507.
The investigators had drawn the patient population for this analysis from 2 CAR studies, CTL019 and CTL119.
CTL019, which had already been completed, employed a murine CAR, and CTL119 is ongoing and uses a humanized CAR.
Of the 60 patients enrolled in CTL019, 56 (93%) achieved a complete response (CR) at day 28, and 100% had a CNS remission. Their 12-month overall survival (OS) was 79%.
“[K]eep in mind, when the study first started,” Dr Talekar said, “the patient population that had been referred to us was patients who had suffered a second or greater relapse or had been refractory to forms of treatment available to them, and the majority had been refractory to multiple therapies.”
The humanized CAR study, CTL119, is divided into 2 cohorts—one with CAR-naïve patients (n=22) and the other a CAR-retreatment arm (n=15) with patients who had received previous CAR therapy and relapsed.
Dr Talekar explained that the humanized CAR was made with the intention of decreasing rejection or loss of persistence of the T cells related to murine antigenicity.
Nine patients (60%) in the CAR-retreatment arm achieved a CR at day 28, and at 6 months, 78% experienced relapse-free survival (RFS) with a median follow-up of 12 months.
All of the CAR-naïve patients achieved CR at day 28, with 86% achieving RFS at 6 months, with a median follow-up of 10 months.
ALL with EM involvement
The investigators identified 10 pediatric patients treated in the murine (n=6) or humanized (n=4) trials who had received CAR therapy for isolated extramedullary disease or for combined bone marrow extramedullary (BM/EM) relapse of ALL.
They defined EM relapse as involvement of a non-CNS site confirmed by imaging with or without pathology within 12 months of CAR T-cell infusion. After infusion, patients had diagnostic imaging performed at 1, 3, 6, 9, and 12 months.
Of the 10 patients, 5 had active EM involvement at the time of infusion, 2 had isolated EM relapse—1 with parotid and multifocal bony lesions and 1 with testis and sinus lesions—and 5 had multiple sites of EM relapse.
The patients had 2 to 4 prior ALL relapses, 2 had prior local radiation to the EM site, and all 10 had received prior bone marrow transplants.
Three patients had an MLL rearrangement, 1 had hypodiploid ALL, and 1 had trisomy 21.
Nine of the 10 patients achieved MRD-negative CR at day 28.
One patient was not evaluable because his disease progressed within 2 weeks of CAR therapy in both the bone marrow and EM site. He died 6 weeks after the infusion.
Five patients evaluated by serial imaging had objective responses. Two had no evidence of EM disease by day 28, 2 had resolution by 3 months, and 1 had continued decrease in the size of her uterine mass at 3 and 6 months. She underwent hysterectomy at 8 months with no evidence of disease on pathology.
Four patients with a prior history of skin or testicular involvement had no evidence of disease by exam at day 28.
Three of the 9 patients relapsed with CD19+ disease. One had skin/medullary involvement and died at 38 months after CAR T-cell infusion. And 2 had medullary disease: 1 died at 17 months and 1 is alive at 28 months.
The remaining 6 patients are alive and well at a median follow-up of 10 months (range, 3 – 16 months) without recurrence of disease.
The investigators therefore concluded that single agent CAR T-cell immunotherapy can induce potent and durable response in patients with EM relapse of their ALL.
CHICAGO—Outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) are dismal, with the probability of event-free survival ranging from 15% to 70% after a first relapse to 15% to 20% after a second relapse.
“So novel therapies are obviously urgently needed,” Mala Kiran Talekar, MD, of the Children's Hospital of Philadelphia in Pennsylvania, affirmed. “And herein comes the role of CAR T cells as a breakthrough therapy for relapsed/refractory pediatric ALL.”
She presented the outcome of chimeric antigen receptor (CAR) T-cell therapy in pediatric patients with non-CNS extramedullary (EM) relapse at the ASCO 2017 Annual meeting as abstract 10507.
The investigators had drawn the patient population for this analysis from 2 CAR studies, CTL019 and CTL119.
CTL019, which had already been completed, employed a murine CAR, and CTL119 is ongoing and uses a humanized CAR.
Of the 60 patients enrolled in CTL019, 56 (93%) achieved a complete response (CR) at day 28, and 100% had a CNS remission. Their 12-month overall survival (OS) was 79%.
“[K]eep in mind, when the study first started,” Dr Talekar said, “the patient population that had been referred to us was patients who had suffered a second or greater relapse or had been refractory to forms of treatment available to them, and the majority had been refractory to multiple therapies.”
The humanized CAR study, CTL119, is divided into 2 cohorts—one with CAR-naïve patients (n=22) and the other a CAR-retreatment arm (n=15) with patients who had received previous CAR therapy and relapsed.
Dr Talekar explained that the humanized CAR was made with the intention of decreasing rejection or loss of persistence of the T cells related to murine antigenicity.
Nine patients (60%) in the CAR-retreatment arm achieved a CR at day 28, and at 6 months, 78% experienced relapse-free survival (RFS) with a median follow-up of 12 months.
All of the CAR-naïve patients achieved CR at day 28, with 86% achieving RFS at 6 months, with a median follow-up of 10 months.
ALL with EM involvement
The investigators identified 10 pediatric patients treated in the murine (n=6) or humanized (n=4) trials who had received CAR therapy for isolated extramedullary disease or for combined bone marrow extramedullary (BM/EM) relapse of ALL.
They defined EM relapse as involvement of a non-CNS site confirmed by imaging with or without pathology within 12 months of CAR T-cell infusion. After infusion, patients had diagnostic imaging performed at 1, 3, 6, 9, and 12 months.
Of the 10 patients, 5 had active EM involvement at the time of infusion, 2 had isolated EM relapse—1 with parotid and multifocal bony lesions and 1 with testis and sinus lesions—and 5 had multiple sites of EM relapse.
The patients had 2 to 4 prior ALL relapses, 2 had prior local radiation to the EM site, and all 10 had received prior bone marrow transplants.
Three patients had an MLL rearrangement, 1 had hypodiploid ALL, and 1 had trisomy 21.
Nine of the 10 patients achieved MRD-negative CR at day 28.
One patient was not evaluable because his disease progressed within 2 weeks of CAR therapy in both the bone marrow and EM site. He died 6 weeks after the infusion.
Five patients evaluated by serial imaging had objective responses. Two had no evidence of EM disease by day 28, 2 had resolution by 3 months, and 1 had continued decrease in the size of her uterine mass at 3 and 6 months. She underwent hysterectomy at 8 months with no evidence of disease on pathology.
Four patients with a prior history of skin or testicular involvement had no evidence of disease by exam at day 28.
Three of the 9 patients relapsed with CD19+ disease. One had skin/medullary involvement and died at 38 months after CAR T-cell infusion. And 2 had medullary disease: 1 died at 17 months and 1 is alive at 28 months.
The remaining 6 patients are alive and well at a median follow-up of 10 months (range, 3 – 16 months) without recurrence of disease.
The investigators therefore concluded that single agent CAR T-cell immunotherapy can induce potent and durable response in patients with EM relapse of their ALL.
Test goes wide and deep to detect free tumor DNA in blood
CHICAGO – An experimental liquid biopsy method plumbs the depths of the genome to detect a broad array of mutations in blood samples that closely correspond to variants in tumors.
The high-intensity method for detecting circulating free DNA (cfDNA) in plasma detected at least one significant genetic variant in samples from 89% of patients with advanced breast, lung, and prostate cancers.
If validated in further studies, the technique could inform more accurate drug selection in patients with refractory disease and eventually may form the basis for plasma-based assays to detect early-stage cancers, said Pedram Razavi, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.
“This novel, high-intensity sequencing assay incorporates an unprecedented combination of depth and breadth of coverage compared to previous assays. High levels of concordance for variants between plasma and tissue provide strong evidence for high rates of tumor DNA detection in plasma,” he said at a press briefing at the annual meeting of the American Society of Clinical Oncology.
The technique also provides important insights into tumor biology, “including first exploration of mutational signatures in the plasma,” he added.
Deep scanning
The high-intensity sequencing method scans for 508 genes in a 2 million base-pair swath of genome, performing 60,000 repeat reads on each genome region to improve the assay’s sensitivity, and deep sequencing allows for detection of rare “needle-in-a-haystack” variants.
Dr. Razavi and his colleagues examined prospectively collected blood and tissues from 161 patients, 124 of whom had samples sufficient for concordance studies.
The samples were collected within 6 weeks of a de novo cancer diagnosis or evidence of disease progression, before the initiation of therapy.
Both cfDNA and genomic data from white blood cells (WBCs) of each patient were sequenced with the aforementioned 508-gene panel covering a broad range of known cancer variants and mutations.
Tumor tissues were sequenced with MSK-IMPACT, a 410 gene assay, with blinding of results in regard to plasma and WBC sequencing. Variants were classified as clonal or subclonal based on tumor sequencing in breast cancer and non–small cell lung cancer (NSCLC).
As noted before, 89% of patients had at least one genetic variant detected in both the tumor and in plasma, including 97% of patients with metastatic breast cancer, 85% of those with NSCLC, and 84% of patients with metastatic prostate cancer.
The investigators identified 864 clonal or subclonal variants in tissue samples from all three of these cancers, and 627 of the variants also were found in plasma.
In addition, 76% of clinically actionable somatic mutations identified in tumors also were found in plasma, which suggests that the high-intensity sequencing technique may be able to identify tumor heterogeneity that is not always evident in single tumor biopsies, Dr. Razavi said.
‘A clear advance’
“The work by Dr. Razavi and colleagues is a clear advance in the field because it surveys for the first time a much broader panel of genes – 508 genes in this case – and it does it with much deeper sequencing, which means it can detect much rarer alterations,” commented ASCO expert John Heymach, MD, PhD, from the University of Texas MD Anderson Cancer Center in Houston.
The study “helps illuminate a path toward a day when we will be using circulating tumor DNA assays for early detection of cancer, and not just for selecting certain therapies,” he added.
“We’re a long way from utilizing liquid biopsy for detecting cancers; already though, we’re seeing some utility of circulating tumor DNA in the domain of identifying novel alterations as a means of segmentation clinical trials,” commented ASCO expert Sumanta Kumar Pal, MD, from City of Hope in Duarte, Calif.
Dr. Heymach and Dr. Pal were not involved in the study, but were invited discussants at the briefing.
The study was funded in part by GRAIL. Dr. Razavi reported institutional research funding from the company. Multiple coauthors are employees of the company.
CHICAGO – An experimental liquid biopsy method plumbs the depths of the genome to detect a broad array of mutations in blood samples that closely correspond to variants in tumors.
The high-intensity method for detecting circulating free DNA (cfDNA) in plasma detected at least one significant genetic variant in samples from 89% of patients with advanced breast, lung, and prostate cancers.
If validated in further studies, the technique could inform more accurate drug selection in patients with refractory disease and eventually may form the basis for plasma-based assays to detect early-stage cancers, said Pedram Razavi, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.
“This novel, high-intensity sequencing assay incorporates an unprecedented combination of depth and breadth of coverage compared to previous assays. High levels of concordance for variants between plasma and tissue provide strong evidence for high rates of tumor DNA detection in plasma,” he said at a press briefing at the annual meeting of the American Society of Clinical Oncology.
The technique also provides important insights into tumor biology, “including first exploration of mutational signatures in the plasma,” he added.
Deep scanning
The high-intensity sequencing method scans for 508 genes in a 2 million base-pair swath of genome, performing 60,000 repeat reads on each genome region to improve the assay’s sensitivity, and deep sequencing allows for detection of rare “needle-in-a-haystack” variants.
Dr. Razavi and his colleagues examined prospectively collected blood and tissues from 161 patients, 124 of whom had samples sufficient for concordance studies.
The samples were collected within 6 weeks of a de novo cancer diagnosis or evidence of disease progression, before the initiation of therapy.
Both cfDNA and genomic data from white blood cells (WBCs) of each patient were sequenced with the aforementioned 508-gene panel covering a broad range of known cancer variants and mutations.
Tumor tissues were sequenced with MSK-IMPACT, a 410 gene assay, with blinding of results in regard to plasma and WBC sequencing. Variants were classified as clonal or subclonal based on tumor sequencing in breast cancer and non–small cell lung cancer (NSCLC).
As noted before, 89% of patients had at least one genetic variant detected in both the tumor and in plasma, including 97% of patients with metastatic breast cancer, 85% of those with NSCLC, and 84% of patients with metastatic prostate cancer.
The investigators identified 864 clonal or subclonal variants in tissue samples from all three of these cancers, and 627 of the variants also were found in plasma.
In addition, 76% of clinically actionable somatic mutations identified in tumors also were found in plasma, which suggests that the high-intensity sequencing technique may be able to identify tumor heterogeneity that is not always evident in single tumor biopsies, Dr. Razavi said.
‘A clear advance’
“The work by Dr. Razavi and colleagues is a clear advance in the field because it surveys for the first time a much broader panel of genes – 508 genes in this case – and it does it with much deeper sequencing, which means it can detect much rarer alterations,” commented ASCO expert John Heymach, MD, PhD, from the University of Texas MD Anderson Cancer Center in Houston.
The study “helps illuminate a path toward a day when we will be using circulating tumor DNA assays for early detection of cancer, and not just for selecting certain therapies,” he added.
“We’re a long way from utilizing liquid biopsy for detecting cancers; already though, we’re seeing some utility of circulating tumor DNA in the domain of identifying novel alterations as a means of segmentation clinical trials,” commented ASCO expert Sumanta Kumar Pal, MD, from City of Hope in Duarte, Calif.
Dr. Heymach and Dr. Pal were not involved in the study, but were invited discussants at the briefing.
The study was funded in part by GRAIL. Dr. Razavi reported institutional research funding from the company. Multiple coauthors are employees of the company.
CHICAGO – An experimental liquid biopsy method plumbs the depths of the genome to detect a broad array of mutations in blood samples that closely correspond to variants in tumors.
The high-intensity method for detecting circulating free DNA (cfDNA) in plasma detected at least one significant genetic variant in samples from 89% of patients with advanced breast, lung, and prostate cancers.
If validated in further studies, the technique could inform more accurate drug selection in patients with refractory disease and eventually may form the basis for plasma-based assays to detect early-stage cancers, said Pedram Razavi, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.
“This novel, high-intensity sequencing assay incorporates an unprecedented combination of depth and breadth of coverage compared to previous assays. High levels of concordance for variants between plasma and tissue provide strong evidence for high rates of tumor DNA detection in plasma,” he said at a press briefing at the annual meeting of the American Society of Clinical Oncology.
The technique also provides important insights into tumor biology, “including first exploration of mutational signatures in the plasma,” he added.
Deep scanning
The high-intensity sequencing method scans for 508 genes in a 2 million base-pair swath of genome, performing 60,000 repeat reads on each genome region to improve the assay’s sensitivity, and deep sequencing allows for detection of rare “needle-in-a-haystack” variants.
Dr. Razavi and his colleagues examined prospectively collected blood and tissues from 161 patients, 124 of whom had samples sufficient for concordance studies.
The samples were collected within 6 weeks of a de novo cancer diagnosis or evidence of disease progression, before the initiation of therapy.
Both cfDNA and genomic data from white blood cells (WBCs) of each patient were sequenced with the aforementioned 508-gene panel covering a broad range of known cancer variants and mutations.
Tumor tissues were sequenced with MSK-IMPACT, a 410 gene assay, with blinding of results in regard to plasma and WBC sequencing. Variants were classified as clonal or subclonal based on tumor sequencing in breast cancer and non–small cell lung cancer (NSCLC).
As noted before, 89% of patients had at least one genetic variant detected in both the tumor and in plasma, including 97% of patients with metastatic breast cancer, 85% of those with NSCLC, and 84% of patients with metastatic prostate cancer.
The investigators identified 864 clonal or subclonal variants in tissue samples from all three of these cancers, and 627 of the variants also were found in plasma.
In addition, 76% of clinically actionable somatic mutations identified in tumors also were found in plasma, which suggests that the high-intensity sequencing technique may be able to identify tumor heterogeneity that is not always evident in single tumor biopsies, Dr. Razavi said.
‘A clear advance’
“The work by Dr. Razavi and colleagues is a clear advance in the field because it surveys for the first time a much broader panel of genes – 508 genes in this case – and it does it with much deeper sequencing, which means it can detect much rarer alterations,” commented ASCO expert John Heymach, MD, PhD, from the University of Texas MD Anderson Cancer Center in Houston.
The study “helps illuminate a path toward a day when we will be using circulating tumor DNA assays for early detection of cancer, and not just for selecting certain therapies,” he added.
“We’re a long way from utilizing liquid biopsy for detecting cancers; already though, we’re seeing some utility of circulating tumor DNA in the domain of identifying novel alterations as a means of segmentation clinical trials,” commented ASCO expert Sumanta Kumar Pal, MD, from City of Hope in Duarte, Calif.
Dr. Heymach and Dr. Pal were not involved in the study, but were invited discussants at the briefing.
The study was funded in part by GRAIL. Dr. Razavi reported institutional research funding from the company. Multiple coauthors are employees of the company.
AT ASCO 2017
Key clinical point: High-intensity sequencing of plasma samples appears capable of detecting actionable tumor mutations in a large proportion of samples.
Major finding: In 89% of patients with advanced cancers, genetic variants were identified in both tumor samples and circulating free DNA testing.
Data source: Prospective study of tissue and plasma samples from 124 patients with non–small cell lung cancer or metastatic breast and prostate cancers.
Disclosures: The study was funded in part by GRAIL. Dr. Razavi reported institutional research funding from the company. Multiple coauthors are employees of the company.
Cost, value of new cancer treatments rarely correlate
New high-priced cancer treatments rarely demonstrate value, compared with the prices being charged for them.
Researchers examined clinical trial data for new treatments using scoring frameworks developed by both the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) that assess the value of cancer therapies by taking into consideration survival gains in relation to toxicity and quality. Findings were simultaneously published online June 2 in The Lancet Oncology (2017 June 2. doi: 10.1016/S1470-2045(17)30415-1) and presented at the annual meeting of the American Society of Clinical Oncology.
One of the findings from the research quantified the magnitude of how much benefit a new treatment offers patients.
“We were able to compare that across different treatments and we were able to calculate the drug cost per month of treatment with each new cancer treatment,” Christopher Booth, MD, of Queen’s University Cancer Research Institute, Kingston, Ont., and one of the report’s authors, said in an interview.
“We looked to see whether there is a relationship between cost and benefit. In most elements of our economy, if something is of higher value and better quality, we often pay more for it as opposed to something that offers less quality or less value,” he continued. “We found that that relationship does not hold true in the world of cancer drugs. In fact, if anything, we saw an inverse association, meaning that the drugs that are the most expensive actually have the smallest benefit for patients. That is probably the most important finding of the work.”
Dr. Booth suggested that this has to do with the fact that value is never a factor in pricing.
“In very general terms, the way that a new drug is priced is effectively the highest price the market will bear,” he said. “There really isn’t an approach currently to price drugs based on the return that they offer to patients and society. There is a conversation under way within the oncology community about whether we need to be shifting that conversation to something perhaps called value-based pricing where treatments that offer greater benefit to patients are priced higher than treatments that offer negligible benefit.”
He also noted that “there is not a lot of incentive for the research community or pharmaceutical companies to identify drugs that have larger and larger benefits, being that the financial return on their investment does not appear to be related to how much benefit the drug offers. If we shifted that conversation, it would hopefully, at least in some way, drive the research community and push us to find treatments that have large or meaningful benefits to patients instead of some of these treatments that are very expensive with important side effects that really offer very small improvements in patient outcomes.”
Dr. Booth continued: “I think it’s inevitable and I think what these score cards are doing, and even though they are not perfect, are getting the conversation into the mainstream and for the first time allowing oncologists and researchers and policy makers to start some kind of comparative analyses looking at one treatment compared to the other in the same disease setting as offering a greater or lesser benefit to patients,” which is an important conversation as health care systems are faced with stretching their limited resources to help the populations they serve.
The other key finding of the report was the lack of correlation between the scores yielded by the ASCO Value Framework and the ESMO Magnitude of Clinical Benefit Scale.
“We looked at a number of randomized trials of new cancer treatments and we scored them using the European approach and the American approach and found that there is actually fairly little agreement between the two systems,” Dr. Booth said.
The cause, he suggested, was tied to differences in methodology between the two systems, though he noted that both frameworks are evolving and “I suspect there will be convergence over time.”
New high-priced cancer treatments rarely demonstrate value, compared with the prices being charged for them.
Researchers examined clinical trial data for new treatments using scoring frameworks developed by both the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) that assess the value of cancer therapies by taking into consideration survival gains in relation to toxicity and quality. Findings were simultaneously published online June 2 in The Lancet Oncology (2017 June 2. doi: 10.1016/S1470-2045(17)30415-1) and presented at the annual meeting of the American Society of Clinical Oncology.
One of the findings from the research quantified the magnitude of how much benefit a new treatment offers patients.
“We were able to compare that across different treatments and we were able to calculate the drug cost per month of treatment with each new cancer treatment,” Christopher Booth, MD, of Queen’s University Cancer Research Institute, Kingston, Ont., and one of the report’s authors, said in an interview.
“We looked to see whether there is a relationship between cost and benefit. In most elements of our economy, if something is of higher value and better quality, we often pay more for it as opposed to something that offers less quality or less value,” he continued. “We found that that relationship does not hold true in the world of cancer drugs. In fact, if anything, we saw an inverse association, meaning that the drugs that are the most expensive actually have the smallest benefit for patients. That is probably the most important finding of the work.”
Dr. Booth suggested that this has to do with the fact that value is never a factor in pricing.
“In very general terms, the way that a new drug is priced is effectively the highest price the market will bear,” he said. “There really isn’t an approach currently to price drugs based on the return that they offer to patients and society. There is a conversation under way within the oncology community about whether we need to be shifting that conversation to something perhaps called value-based pricing where treatments that offer greater benefit to patients are priced higher than treatments that offer negligible benefit.”
He also noted that “there is not a lot of incentive for the research community or pharmaceutical companies to identify drugs that have larger and larger benefits, being that the financial return on their investment does not appear to be related to how much benefit the drug offers. If we shifted that conversation, it would hopefully, at least in some way, drive the research community and push us to find treatments that have large or meaningful benefits to patients instead of some of these treatments that are very expensive with important side effects that really offer very small improvements in patient outcomes.”
Dr. Booth continued: “I think it’s inevitable and I think what these score cards are doing, and even though they are not perfect, are getting the conversation into the mainstream and for the first time allowing oncologists and researchers and policy makers to start some kind of comparative analyses looking at one treatment compared to the other in the same disease setting as offering a greater or lesser benefit to patients,” which is an important conversation as health care systems are faced with stretching their limited resources to help the populations they serve.
The other key finding of the report was the lack of correlation between the scores yielded by the ASCO Value Framework and the ESMO Magnitude of Clinical Benefit Scale.
“We looked at a number of randomized trials of new cancer treatments and we scored them using the European approach and the American approach and found that there is actually fairly little agreement between the two systems,” Dr. Booth said.
The cause, he suggested, was tied to differences in methodology between the two systems, though he noted that both frameworks are evolving and “I suspect there will be convergence over time.”
New high-priced cancer treatments rarely demonstrate value, compared with the prices being charged for them.
Researchers examined clinical trial data for new treatments using scoring frameworks developed by both the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) that assess the value of cancer therapies by taking into consideration survival gains in relation to toxicity and quality. Findings were simultaneously published online June 2 in The Lancet Oncology (2017 June 2. doi: 10.1016/S1470-2045(17)30415-1) and presented at the annual meeting of the American Society of Clinical Oncology.
One of the findings from the research quantified the magnitude of how much benefit a new treatment offers patients.
“We were able to compare that across different treatments and we were able to calculate the drug cost per month of treatment with each new cancer treatment,” Christopher Booth, MD, of Queen’s University Cancer Research Institute, Kingston, Ont., and one of the report’s authors, said in an interview.
“We looked to see whether there is a relationship between cost and benefit. In most elements of our economy, if something is of higher value and better quality, we often pay more for it as opposed to something that offers less quality or less value,” he continued. “We found that that relationship does not hold true in the world of cancer drugs. In fact, if anything, we saw an inverse association, meaning that the drugs that are the most expensive actually have the smallest benefit for patients. That is probably the most important finding of the work.”
Dr. Booth suggested that this has to do with the fact that value is never a factor in pricing.
“In very general terms, the way that a new drug is priced is effectively the highest price the market will bear,” he said. “There really isn’t an approach currently to price drugs based on the return that they offer to patients and society. There is a conversation under way within the oncology community about whether we need to be shifting that conversation to something perhaps called value-based pricing where treatments that offer greater benefit to patients are priced higher than treatments that offer negligible benefit.”
He also noted that “there is not a lot of incentive for the research community or pharmaceutical companies to identify drugs that have larger and larger benefits, being that the financial return on their investment does not appear to be related to how much benefit the drug offers. If we shifted that conversation, it would hopefully, at least in some way, drive the research community and push us to find treatments that have large or meaningful benefits to patients instead of some of these treatments that are very expensive with important side effects that really offer very small improvements in patient outcomes.”
Dr. Booth continued: “I think it’s inevitable and I think what these score cards are doing, and even though they are not perfect, are getting the conversation into the mainstream and for the first time allowing oncologists and researchers and policy makers to start some kind of comparative analyses looking at one treatment compared to the other in the same disease setting as offering a greater or lesser benefit to patients,” which is an important conversation as health care systems are faced with stretching their limited resources to help the populations they serve.
The other key finding of the report was the lack of correlation between the scores yielded by the ASCO Value Framework and the ESMO Magnitude of Clinical Benefit Scale.
“We looked at a number of randomized trials of new cancer treatments and we scored them using the European approach and the American approach and found that there is actually fairly little agreement between the two systems,” Dr. Booth said.
The cause, he suggested, was tied to differences in methodology between the two systems, though he noted that both frameworks are evolving and “I suspect there will be convergence over time.”
FROM ASCO 2017
VIDEO: Olaparib improves outlook in women with BRCA-related HER2-negative MBC
CHICAGO – Compared with single-agent chemotherapy of the oncologist’s choice, the PARP inhibitor olaparib reduced the risk of progression or death by 42% in women with BRCA-related HER2-negative metastatic breast cancer, the OlympiAD trialists reported in a plenary session at the annual meeting of the American Society of Clinical Oncology.
Lead author Mark E. Robson, MD, of Memorial Sloan Kettering Cancer Center, New York, discussed findings of the randomized phase III trial, as well as strategies for building on the trial’s success and what the future holds for this class of agents in breast cancer.
Dr. Robson disclosed that he has a consulting or advisory role with McKesson and AstraZeneca; receives travel, accommodations, and/or expenses from AstraZeneca; receives honoraria from AstraZeneca; and receives research funding (institutional) from AstraZeneca, Abbvie, Myriad Genetics, Biomarin, Medivation, and Tesaro. The trial was funded by AstraZeneca.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Compared with single-agent chemotherapy of the oncologist’s choice, the PARP inhibitor olaparib reduced the risk of progression or death by 42% in women with BRCA-related HER2-negative metastatic breast cancer, the OlympiAD trialists reported in a plenary session at the annual meeting of the American Society of Clinical Oncology.
Lead author Mark E. Robson, MD, of Memorial Sloan Kettering Cancer Center, New York, discussed findings of the randomized phase III trial, as well as strategies for building on the trial’s success and what the future holds for this class of agents in breast cancer.
Dr. Robson disclosed that he has a consulting or advisory role with McKesson and AstraZeneca; receives travel, accommodations, and/or expenses from AstraZeneca; receives honoraria from AstraZeneca; and receives research funding (institutional) from AstraZeneca, Abbvie, Myriad Genetics, Biomarin, Medivation, and Tesaro. The trial was funded by AstraZeneca.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Compared with single-agent chemotherapy of the oncologist’s choice, the PARP inhibitor olaparib reduced the risk of progression or death by 42% in women with BRCA-related HER2-negative metastatic breast cancer, the OlympiAD trialists reported in a plenary session at the annual meeting of the American Society of Clinical Oncology.
Lead author Mark E. Robson, MD, of Memorial Sloan Kettering Cancer Center, New York, discussed findings of the randomized phase III trial, as well as strategies for building on the trial’s success and what the future holds for this class of agents in breast cancer.
Dr. Robson disclosed that he has a consulting or advisory role with McKesson and AstraZeneca; receives travel, accommodations, and/or expenses from AstraZeneca; receives honoraria from AstraZeneca; and receives research funding (institutional) from AstraZeneca, Abbvie, Myriad Genetics, Biomarin, Medivation, and Tesaro. The trial was funded by AstraZeneca.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ASCO 2017
VIDEO: Abiraterone improves survival in high-risk prostate cancer
CHICAGO – Adding abiraterone acetate plus prednisone to androgen deprivation therapy in hormone-naive high-risk prostate cancer patients significantly improves overall survival, according to “practice-changing” results from the phase III LATITUDE trial and the multiarm, multistage STAMPEDE trial.
In the double-blind, randomized, placebo-controlled LATITUDE trial, 597 patients with newly diagnosed high-risk metastatic prostate cancer who received 1,000 mg of abiraterone acetate daily plus 5 mg of prednisone daily in addition to androgen deprivation therapy experienced a 38% reduction in the risk of death and a 53% reduction in the risk of radiographic progression or death at a median follow-up of 30.4 months, compared with 602 such patients who received placebo and androgen deprivation, Karim Fizazi, MD, PhD, of the Institut Gustave Roussy, Villejuif, France, reported at the annual meeting of the American Society of Clinical Oncology.
Significant improvements also were seen in the treatment vs. placebo group for all secondary endpoints, including time to prostate-specific-antigen progression (hazard ratio, 0.30), time to pain progression (HR, 0.70), time to next symptomatic skeletal event (HR, 0.70), time to chemotherapy (HR, 0.44), and time to subsequent prostate cancer therapy (HR, 0.42), Dr. Fizazi said.
He discussed the findings, including side effects, and ongoing and future studies, in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“Based on these findings, I believe that using abiraterone up front, together with androgen deprivation therapy, will become the next standard of care for these men,” he said.
Similarly, in the STAMPEDE trial, abiraterone acetate plus prednisone was associated with significantly improved overall survival in 960 high-risk prostate cancer patients starting hormone therapy, compared with 957 such patients receiving placebo and standard-of-care hormone therapy, according to Nicholas D. James, BSc MBBS, PhD, of the Institute of Cancer and Genomic Sciences, University of Birmingham, England.
“Overall, we’ve got about a 30% improvement in survival times for the upfront use of abiraterone. For our metastatic patients, we haven’t reached the median survival yet for the abiraterone patients, but it’s around 3.5 years median survival in the control arm, and we’re projecting that’s going to go up to 6.5 or 7 years in the abiraterone patients,” he said in a video interview, adding that he and his colleagues think this will be one of the biggest survival gains ever reported in adults in such a setting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. James also discussed findings with respect to secondary endpoints, including a 70% improvement in failure-free survival in the treatment vs. placebo group – an improvement that he called an “absolutely spectacularly big gain” – and skeletal-related events, which decreased by 55% in the treatment group.
Both investigators discussed ongoing and recently completed studies that could shed additional light on the use of abiraterone in prostate cancer patients, including plans to look at the effects of giving both abiraterone and docetaxel together.
“My prediction will be that we will be giving both treatments in due course,” Dr. James said, adding, “I think these findings will certainly be practice changing.”
CHICAGO – Adding abiraterone acetate plus prednisone to androgen deprivation therapy in hormone-naive high-risk prostate cancer patients significantly improves overall survival, according to “practice-changing” results from the phase III LATITUDE trial and the multiarm, multistage STAMPEDE trial.
In the double-blind, randomized, placebo-controlled LATITUDE trial, 597 patients with newly diagnosed high-risk metastatic prostate cancer who received 1,000 mg of abiraterone acetate daily plus 5 mg of prednisone daily in addition to androgen deprivation therapy experienced a 38% reduction in the risk of death and a 53% reduction in the risk of radiographic progression or death at a median follow-up of 30.4 months, compared with 602 such patients who received placebo and androgen deprivation, Karim Fizazi, MD, PhD, of the Institut Gustave Roussy, Villejuif, France, reported at the annual meeting of the American Society of Clinical Oncology.
Significant improvements also were seen in the treatment vs. placebo group for all secondary endpoints, including time to prostate-specific-antigen progression (hazard ratio, 0.30), time to pain progression (HR, 0.70), time to next symptomatic skeletal event (HR, 0.70), time to chemotherapy (HR, 0.44), and time to subsequent prostate cancer therapy (HR, 0.42), Dr. Fizazi said.
He discussed the findings, including side effects, and ongoing and future studies, in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“Based on these findings, I believe that using abiraterone up front, together with androgen deprivation therapy, will become the next standard of care for these men,” he said.
Similarly, in the STAMPEDE trial, abiraterone acetate plus prednisone was associated with significantly improved overall survival in 960 high-risk prostate cancer patients starting hormone therapy, compared with 957 such patients receiving placebo and standard-of-care hormone therapy, according to Nicholas D. James, BSc MBBS, PhD, of the Institute of Cancer and Genomic Sciences, University of Birmingham, England.
“Overall, we’ve got about a 30% improvement in survival times for the upfront use of abiraterone. For our metastatic patients, we haven’t reached the median survival yet for the abiraterone patients, but it’s around 3.5 years median survival in the control arm, and we’re projecting that’s going to go up to 6.5 or 7 years in the abiraterone patients,” he said in a video interview, adding that he and his colleagues think this will be one of the biggest survival gains ever reported in adults in such a setting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. James also discussed findings with respect to secondary endpoints, including a 70% improvement in failure-free survival in the treatment vs. placebo group – an improvement that he called an “absolutely spectacularly big gain” – and skeletal-related events, which decreased by 55% in the treatment group.
Both investigators discussed ongoing and recently completed studies that could shed additional light on the use of abiraterone in prostate cancer patients, including plans to look at the effects of giving both abiraterone and docetaxel together.
“My prediction will be that we will be giving both treatments in due course,” Dr. James said, adding, “I think these findings will certainly be practice changing.”
CHICAGO – Adding abiraterone acetate plus prednisone to androgen deprivation therapy in hormone-naive high-risk prostate cancer patients significantly improves overall survival, according to “practice-changing” results from the phase III LATITUDE trial and the multiarm, multistage STAMPEDE trial.
In the double-blind, randomized, placebo-controlled LATITUDE trial, 597 patients with newly diagnosed high-risk metastatic prostate cancer who received 1,000 mg of abiraterone acetate daily plus 5 mg of prednisone daily in addition to androgen deprivation therapy experienced a 38% reduction in the risk of death and a 53% reduction in the risk of radiographic progression or death at a median follow-up of 30.4 months, compared with 602 such patients who received placebo and androgen deprivation, Karim Fizazi, MD, PhD, of the Institut Gustave Roussy, Villejuif, France, reported at the annual meeting of the American Society of Clinical Oncology.
Significant improvements also were seen in the treatment vs. placebo group for all secondary endpoints, including time to prostate-specific-antigen progression (hazard ratio, 0.30), time to pain progression (HR, 0.70), time to next symptomatic skeletal event (HR, 0.70), time to chemotherapy (HR, 0.44), and time to subsequent prostate cancer therapy (HR, 0.42), Dr. Fizazi said.
He discussed the findings, including side effects, and ongoing and future studies, in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“Based on these findings, I believe that using abiraterone up front, together with androgen deprivation therapy, will become the next standard of care for these men,” he said.
Similarly, in the STAMPEDE trial, abiraterone acetate plus prednisone was associated with significantly improved overall survival in 960 high-risk prostate cancer patients starting hormone therapy, compared with 957 such patients receiving placebo and standard-of-care hormone therapy, according to Nicholas D. James, BSc MBBS, PhD, of the Institute of Cancer and Genomic Sciences, University of Birmingham, England.
“Overall, we’ve got about a 30% improvement in survival times for the upfront use of abiraterone. For our metastatic patients, we haven’t reached the median survival yet for the abiraterone patients, but it’s around 3.5 years median survival in the control arm, and we’re projecting that’s going to go up to 6.5 or 7 years in the abiraterone patients,” he said in a video interview, adding that he and his colleagues think this will be one of the biggest survival gains ever reported in adults in such a setting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. James also discussed findings with respect to secondary endpoints, including a 70% improvement in failure-free survival in the treatment vs. placebo group – an improvement that he called an “absolutely spectacularly big gain” – and skeletal-related events, which decreased by 55% in the treatment group.
Both investigators discussed ongoing and recently completed studies that could shed additional light on the use of abiraterone in prostate cancer patients, including plans to look at the effects of giving both abiraterone and docetaxel together.
“My prediction will be that we will be giving both treatments in due course,” Dr. James said, adding, “I think these findings will certainly be practice changing.”
AT ASCO 2017
Interventions ease cancer-related stress, depression
CHICAGO – Clinicians have gotten much better in recent decades at helping patients cope with physical side effects from cancer care, but mental health interventions aimed at easing stress and fear are often absent or, at best, an afterthought.
As three new studies show, however, early psychological interventions can both improve the quality of life for patients with cancer and enhance clinical outcomes.
For example, an online stress management program dubbed STREAM, developed jointly by oncologists and psychologists, was associated with significantly better quality of life and lower levels of distress for patients 2 months after a new cancer diagnosis, compared with controls who had not yet used it, reported Viviane Hess, MD, a medical oncologist at the University Hospital of Basel (Switzerland).
“From randomized controlled trials, we know that cognitive behavioral therapies are effective in mediating distress. However, the majority of cancer patients lack psychological support, due to both barriers on the patients’ side and lack of resources on the providers’ side,” she said at a briefing at the annual meeting of the American Society of Clinical Oncology.
Other studies presented in the briefing show that psychological interventions can significantly reduce patient anxieties about the possibility of cancer recurrence and help relieve depressive symptoms for at least 6 months among patients with advanced cancers.
STREAM
Dr. Hess and her colleagues conducted a prospective, wait-list controlled trial for patients who had started therapy for a newly diagnosed cancer within the past 12 weeks. The patients were randomized to either immediate use of an online psychological intervention or to a delayed start.
The investigators chose a web-based intervention because a majority of patients with cancer already use the Internet for information, and because Internet interventions can overcome barriers of time and distance, with results comparable to those seen with face-to-face interventions, Dr. Hess said.
The intervention consisted of eight weekly sessions based on approaches used in cognitive behavioral therapy, with focus on bodily reactions to stress, cognitive stress reduction, feelings, and social interactions. Each of the eight sessions focused on a single topic. Patients were given written and audio information about each topic and then were asked to perform exercises and complete questionnaires.
For this “minimal contact” intervention, psychologists based in Basel reviewed each patient’s progress weekly and gave written feedback personalized for that patient via a secure online portal.
In all, 129 patients were randomized (65 to the intervention and 64 controls). The majority were women treated with curative intent for early-stage breast cancer. Patients newly diagnosed with lung, ovarian, and gastrointestinal cancers, as well as melanoma and lymphoma, also were included.
Patients in both the active intervention and control groups were assessed at baseline and at 2 months with three quality-of-life measures: the FACIT-F (Functional Assessment of Chronic Illness Therapy Fatigue subscale), DT (Distress Thermometer), and HADS (Hospital Anxiety and Depression Scale).
At 2 months, the mean FACIT-F score for patients in both the intervention and control groups increased, indicating an improved quality of life, but the change was significantly greater for patients in the intervention group (mean 8.59 points vs. controls; P = .0032). There was also a significant decrease in the DT scale from 6 points at baseline to 4 points at 2 months among patients randomized to the intervention, but no change among controls. There were no significant differences in either anxiety or depression between the groups, however.
“Most oncologists, particularly when we’re meeting patients for the first time and starting on curative intent therapy, it is assumed there is a level of distress … but we assume that that level of distress will fall naturally as we start them on therapy,” commented ASCO expert Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center in Boston, who was not involved in the study.
“What Dr. Hess is showing is that not only do they have distress, but it’s significant distress,” he said, adding that the study shows that online tools can be effective at providing support, and that the ease of access can help patients who might otherwise never meet with a mental health professional.
Recurrence fears assuaged
In a separate study, investigators from Australia reported results of a randomized phase II trial showing that an intervention called Conquer Fear was effective at lowering fear of recurrence among patients with successfully treated stage I-III breast, colorectal, or melanoma cancers who reported a high level of fear of recurrence.
“Fear of cancer recurrence is associated with poorer quality of life, greater distress, lack of planning for the future, avoidance or excessive use of screening, and greater health care utilization,” said Jane MacNeil Beith, MD, PhD, a medical oncologist at the University of Sydney.
Dr. Beith and her colleagues randomly assigned 222 patients to either the Conquer Fear intervention or relaxation training (control group).
Patients assigned to the control group received five 1-hour individual, face-to-face relaxation sessions over 10 weeks. The sessions included muscle relaxation, meditative relaxation, and visualization and quick relaxation techniques taught by trained study instructors. Patients in each group received instructions for home-based relaxation techniques.
The Conquer Fear intervention is intended to help patients with values clarification, detached mindfulness (focusing on the moment), attention training, meta-cognitive therapy (worry or not worry), and a behavioral contract to ensure appropriate follow-up.
They measured fear of recurrence using the validated 42-item Fear of Cancer Recurrence Inventory (FCRI), which scores fear on a scale of 0-168, with higher scores indicating higher levels of fear, Dr. Beith said.
The mean baseline FCRI scores were 82.7 for patients assigned to the intervention and 85.7 in controls.
Participants in both groups had improvement of all outcomes, but patients in the active intervention group had significantly lower FCRI total scores at the end of the intervention and at 3 and 6 months of follow-up. The severity of fear of recurrence was also lower among patients in the intervention group immediately afterward and at 3 months, but not at 6 months, she reported.
“I applaud Dr. Beith for her trial, particularly because we as oncologists have only about 15 minutes with our patients, and the assessments for our patients, even in follow-up, for the most part concentrate on cancer-related outcomes, because that’s what our patients want to know. They want to know if they’re fine, or they want to know, is their cancer back,” Dr. Dizon commented.
The study demonstrates fear of recurrence is real, but that there are also interventions that can help patients reduce those fears, he said.
CALM
In a third study, Gary Rodin, MD, from the department of supportive care at Princess Margaret Cancer Centre in Toronto, and his colleagues reported that a brief psychological intervention with the acronym CALM (for Managing Cancer and Living Meaningfully) was associated with a “clinically meaningful” reduction in depressive symptoms in patients with advanced cancer.
Patients in CALM receive three to six individual sessions delivered over 3-6 months. The program helps patients cope with symptom management and improve communications with health care providers, understand changes in themselves and their relations with others, find a personal sense of meaning and purpose, and learn to live with thoughts of the future and mortality, Dr. Rodin explained.
In a clinical trial, 52% of the 151 patients randomized to the intervention had clinically important reductions in depressive symptoms at 3 months, compared with 33% of controls assigned to usual care. At 6 months, the respective reductions in depressive symptoms were 64% vs. 35%.
The intervention also was effective at preventing depression among 137 patients without depressive symptoms at baseline. In this group, 13% of patients who received the CALM intervention had depressive symptoms at 3 months, compared with 30% of controls.
In addition, patients who received CALM support at both 3 and 6 months said they were better prepared for the end of life, reported that they had greater opportunity to talk about their concerns for the future, were less frightened, and said they had greater ability to express and manage their feelings. At 6 months these effects were strengthened, and the CALM group also felt more able to understand their cancer experience, deal with changes in relationships as a result of cancer, explore ways of communicating with their health care team and family, and clarify their values and beliefs.
“The intervention addresses both the practical problems that people face, and there are many – How do I manage my pain? My symptoms? – but also the profound problems and issues that people face – What is the meaning of my life? – when having a terminal diagnosis, for instance,” he said.
The investigators are currently establishing a global network to train health professionals in the delivery of CALM, and to evaluate the program’s effectiveness in different clinical settings and cultures, he said.
The STREAM study was institutionally supported. Dr. Hess disclosed travel and accommodations from CSL Behring. The Conquer Fear study was funded by Cancer Australia, beyondBlue, and the Australian National Breast Cancer Foundation. Dr. Beith reported no relevant disclosures. The CALM study was supported by the Canadian Institute of Health Research. Dr. Rodin reported no relevant disclosures.
CHICAGO – Clinicians have gotten much better in recent decades at helping patients cope with physical side effects from cancer care, but mental health interventions aimed at easing stress and fear are often absent or, at best, an afterthought.
As three new studies show, however, early psychological interventions can both improve the quality of life for patients with cancer and enhance clinical outcomes.
For example, an online stress management program dubbed STREAM, developed jointly by oncologists and psychologists, was associated with significantly better quality of life and lower levels of distress for patients 2 months after a new cancer diagnosis, compared with controls who had not yet used it, reported Viviane Hess, MD, a medical oncologist at the University Hospital of Basel (Switzerland).
“From randomized controlled trials, we know that cognitive behavioral therapies are effective in mediating distress. However, the majority of cancer patients lack psychological support, due to both barriers on the patients’ side and lack of resources on the providers’ side,” she said at a briefing at the annual meeting of the American Society of Clinical Oncology.
Other studies presented in the briefing show that psychological interventions can significantly reduce patient anxieties about the possibility of cancer recurrence and help relieve depressive symptoms for at least 6 months among patients with advanced cancers.
STREAM
Dr. Hess and her colleagues conducted a prospective, wait-list controlled trial for patients who had started therapy for a newly diagnosed cancer within the past 12 weeks. The patients were randomized to either immediate use of an online psychological intervention or to a delayed start.
The investigators chose a web-based intervention because a majority of patients with cancer already use the Internet for information, and because Internet interventions can overcome barriers of time and distance, with results comparable to those seen with face-to-face interventions, Dr. Hess said.
The intervention consisted of eight weekly sessions based on approaches used in cognitive behavioral therapy, with focus on bodily reactions to stress, cognitive stress reduction, feelings, and social interactions. Each of the eight sessions focused on a single topic. Patients were given written and audio information about each topic and then were asked to perform exercises and complete questionnaires.
For this “minimal contact” intervention, psychologists based in Basel reviewed each patient’s progress weekly and gave written feedback personalized for that patient via a secure online portal.
In all, 129 patients were randomized (65 to the intervention and 64 controls). The majority were women treated with curative intent for early-stage breast cancer. Patients newly diagnosed with lung, ovarian, and gastrointestinal cancers, as well as melanoma and lymphoma, also were included.
Patients in both the active intervention and control groups were assessed at baseline and at 2 months with three quality-of-life measures: the FACIT-F (Functional Assessment of Chronic Illness Therapy Fatigue subscale), DT (Distress Thermometer), and HADS (Hospital Anxiety and Depression Scale).
At 2 months, the mean FACIT-F score for patients in both the intervention and control groups increased, indicating an improved quality of life, but the change was significantly greater for patients in the intervention group (mean 8.59 points vs. controls; P = .0032). There was also a significant decrease in the DT scale from 6 points at baseline to 4 points at 2 months among patients randomized to the intervention, but no change among controls. There were no significant differences in either anxiety or depression between the groups, however.
“Most oncologists, particularly when we’re meeting patients for the first time and starting on curative intent therapy, it is assumed there is a level of distress … but we assume that that level of distress will fall naturally as we start them on therapy,” commented ASCO expert Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center in Boston, who was not involved in the study.
“What Dr. Hess is showing is that not only do they have distress, but it’s significant distress,” he said, adding that the study shows that online tools can be effective at providing support, and that the ease of access can help patients who might otherwise never meet with a mental health professional.
Recurrence fears assuaged
In a separate study, investigators from Australia reported results of a randomized phase II trial showing that an intervention called Conquer Fear was effective at lowering fear of recurrence among patients with successfully treated stage I-III breast, colorectal, or melanoma cancers who reported a high level of fear of recurrence.
“Fear of cancer recurrence is associated with poorer quality of life, greater distress, lack of planning for the future, avoidance or excessive use of screening, and greater health care utilization,” said Jane MacNeil Beith, MD, PhD, a medical oncologist at the University of Sydney.
Dr. Beith and her colleagues randomly assigned 222 patients to either the Conquer Fear intervention or relaxation training (control group).
Patients assigned to the control group received five 1-hour individual, face-to-face relaxation sessions over 10 weeks. The sessions included muscle relaxation, meditative relaxation, and visualization and quick relaxation techniques taught by trained study instructors. Patients in each group received instructions for home-based relaxation techniques.
The Conquer Fear intervention is intended to help patients with values clarification, detached mindfulness (focusing on the moment), attention training, meta-cognitive therapy (worry or not worry), and a behavioral contract to ensure appropriate follow-up.
They measured fear of recurrence using the validated 42-item Fear of Cancer Recurrence Inventory (FCRI), which scores fear on a scale of 0-168, with higher scores indicating higher levels of fear, Dr. Beith said.
The mean baseline FCRI scores were 82.7 for patients assigned to the intervention and 85.7 in controls.
Participants in both groups had improvement of all outcomes, but patients in the active intervention group had significantly lower FCRI total scores at the end of the intervention and at 3 and 6 months of follow-up. The severity of fear of recurrence was also lower among patients in the intervention group immediately afterward and at 3 months, but not at 6 months, she reported.
“I applaud Dr. Beith for her trial, particularly because we as oncologists have only about 15 minutes with our patients, and the assessments for our patients, even in follow-up, for the most part concentrate on cancer-related outcomes, because that’s what our patients want to know. They want to know if they’re fine, or they want to know, is their cancer back,” Dr. Dizon commented.
The study demonstrates fear of recurrence is real, but that there are also interventions that can help patients reduce those fears, he said.
CALM
In a third study, Gary Rodin, MD, from the department of supportive care at Princess Margaret Cancer Centre in Toronto, and his colleagues reported that a brief psychological intervention with the acronym CALM (for Managing Cancer and Living Meaningfully) was associated with a “clinically meaningful” reduction in depressive symptoms in patients with advanced cancer.
Patients in CALM receive three to six individual sessions delivered over 3-6 months. The program helps patients cope with symptom management and improve communications with health care providers, understand changes in themselves and their relations with others, find a personal sense of meaning and purpose, and learn to live with thoughts of the future and mortality, Dr. Rodin explained.
In a clinical trial, 52% of the 151 patients randomized to the intervention had clinically important reductions in depressive symptoms at 3 months, compared with 33% of controls assigned to usual care. At 6 months, the respective reductions in depressive symptoms were 64% vs. 35%.
The intervention also was effective at preventing depression among 137 patients without depressive symptoms at baseline. In this group, 13% of patients who received the CALM intervention had depressive symptoms at 3 months, compared with 30% of controls.
In addition, patients who received CALM support at both 3 and 6 months said they were better prepared for the end of life, reported that they had greater opportunity to talk about their concerns for the future, were less frightened, and said they had greater ability to express and manage their feelings. At 6 months these effects were strengthened, and the CALM group also felt more able to understand their cancer experience, deal with changes in relationships as a result of cancer, explore ways of communicating with their health care team and family, and clarify their values and beliefs.
“The intervention addresses both the practical problems that people face, and there are many – How do I manage my pain? My symptoms? – but also the profound problems and issues that people face – What is the meaning of my life? – when having a terminal diagnosis, for instance,” he said.
The investigators are currently establishing a global network to train health professionals in the delivery of CALM, and to evaluate the program’s effectiveness in different clinical settings and cultures, he said.
The STREAM study was institutionally supported. Dr. Hess disclosed travel and accommodations from CSL Behring. The Conquer Fear study was funded by Cancer Australia, beyondBlue, and the Australian National Breast Cancer Foundation. Dr. Beith reported no relevant disclosures. The CALM study was supported by the Canadian Institute of Health Research. Dr. Rodin reported no relevant disclosures.
CHICAGO – Clinicians have gotten much better in recent decades at helping patients cope with physical side effects from cancer care, but mental health interventions aimed at easing stress and fear are often absent or, at best, an afterthought.
As three new studies show, however, early psychological interventions can both improve the quality of life for patients with cancer and enhance clinical outcomes.
For example, an online stress management program dubbed STREAM, developed jointly by oncologists and psychologists, was associated with significantly better quality of life and lower levels of distress for patients 2 months after a new cancer diagnosis, compared with controls who had not yet used it, reported Viviane Hess, MD, a medical oncologist at the University Hospital of Basel (Switzerland).
“From randomized controlled trials, we know that cognitive behavioral therapies are effective in mediating distress. However, the majority of cancer patients lack psychological support, due to both barriers on the patients’ side and lack of resources on the providers’ side,” she said at a briefing at the annual meeting of the American Society of Clinical Oncology.
Other studies presented in the briefing show that psychological interventions can significantly reduce patient anxieties about the possibility of cancer recurrence and help relieve depressive symptoms for at least 6 months among patients with advanced cancers.
STREAM
Dr. Hess and her colleagues conducted a prospective, wait-list controlled trial for patients who had started therapy for a newly diagnosed cancer within the past 12 weeks. The patients were randomized to either immediate use of an online psychological intervention or to a delayed start.
The investigators chose a web-based intervention because a majority of patients with cancer already use the Internet for information, and because Internet interventions can overcome barriers of time and distance, with results comparable to those seen with face-to-face interventions, Dr. Hess said.
The intervention consisted of eight weekly sessions based on approaches used in cognitive behavioral therapy, with focus on bodily reactions to stress, cognitive stress reduction, feelings, and social interactions. Each of the eight sessions focused on a single topic. Patients were given written and audio information about each topic and then were asked to perform exercises and complete questionnaires.
For this “minimal contact” intervention, psychologists based in Basel reviewed each patient’s progress weekly and gave written feedback personalized for that patient via a secure online portal.
In all, 129 patients were randomized (65 to the intervention and 64 controls). The majority were women treated with curative intent for early-stage breast cancer. Patients newly diagnosed with lung, ovarian, and gastrointestinal cancers, as well as melanoma and lymphoma, also were included.
Patients in both the active intervention and control groups were assessed at baseline and at 2 months with three quality-of-life measures: the FACIT-F (Functional Assessment of Chronic Illness Therapy Fatigue subscale), DT (Distress Thermometer), and HADS (Hospital Anxiety and Depression Scale).
At 2 months, the mean FACIT-F score for patients in both the intervention and control groups increased, indicating an improved quality of life, but the change was significantly greater for patients in the intervention group (mean 8.59 points vs. controls; P = .0032). There was also a significant decrease in the DT scale from 6 points at baseline to 4 points at 2 months among patients randomized to the intervention, but no change among controls. There were no significant differences in either anxiety or depression between the groups, however.
“Most oncologists, particularly when we’re meeting patients for the first time and starting on curative intent therapy, it is assumed there is a level of distress … but we assume that that level of distress will fall naturally as we start them on therapy,” commented ASCO expert Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center in Boston, who was not involved in the study.
“What Dr. Hess is showing is that not only do they have distress, but it’s significant distress,” he said, adding that the study shows that online tools can be effective at providing support, and that the ease of access can help patients who might otherwise never meet with a mental health professional.
Recurrence fears assuaged
In a separate study, investigators from Australia reported results of a randomized phase II trial showing that an intervention called Conquer Fear was effective at lowering fear of recurrence among patients with successfully treated stage I-III breast, colorectal, or melanoma cancers who reported a high level of fear of recurrence.
“Fear of cancer recurrence is associated with poorer quality of life, greater distress, lack of planning for the future, avoidance or excessive use of screening, and greater health care utilization,” said Jane MacNeil Beith, MD, PhD, a medical oncologist at the University of Sydney.
Dr. Beith and her colleagues randomly assigned 222 patients to either the Conquer Fear intervention or relaxation training (control group).
Patients assigned to the control group received five 1-hour individual, face-to-face relaxation sessions over 10 weeks. The sessions included muscle relaxation, meditative relaxation, and visualization and quick relaxation techniques taught by trained study instructors. Patients in each group received instructions for home-based relaxation techniques.
The Conquer Fear intervention is intended to help patients with values clarification, detached mindfulness (focusing on the moment), attention training, meta-cognitive therapy (worry or not worry), and a behavioral contract to ensure appropriate follow-up.
They measured fear of recurrence using the validated 42-item Fear of Cancer Recurrence Inventory (FCRI), which scores fear on a scale of 0-168, with higher scores indicating higher levels of fear, Dr. Beith said.
The mean baseline FCRI scores were 82.7 for patients assigned to the intervention and 85.7 in controls.
Participants in both groups had improvement of all outcomes, but patients in the active intervention group had significantly lower FCRI total scores at the end of the intervention and at 3 and 6 months of follow-up. The severity of fear of recurrence was also lower among patients in the intervention group immediately afterward and at 3 months, but not at 6 months, she reported.
“I applaud Dr. Beith for her trial, particularly because we as oncologists have only about 15 minutes with our patients, and the assessments for our patients, even in follow-up, for the most part concentrate on cancer-related outcomes, because that’s what our patients want to know. They want to know if they’re fine, or they want to know, is their cancer back,” Dr. Dizon commented.
The study demonstrates fear of recurrence is real, but that there are also interventions that can help patients reduce those fears, he said.
CALM
In a third study, Gary Rodin, MD, from the department of supportive care at Princess Margaret Cancer Centre in Toronto, and his colleagues reported that a brief psychological intervention with the acronym CALM (for Managing Cancer and Living Meaningfully) was associated with a “clinically meaningful” reduction in depressive symptoms in patients with advanced cancer.
Patients in CALM receive three to six individual sessions delivered over 3-6 months. The program helps patients cope with symptom management and improve communications with health care providers, understand changes in themselves and their relations with others, find a personal sense of meaning and purpose, and learn to live with thoughts of the future and mortality, Dr. Rodin explained.
In a clinical trial, 52% of the 151 patients randomized to the intervention had clinically important reductions in depressive symptoms at 3 months, compared with 33% of controls assigned to usual care. At 6 months, the respective reductions in depressive symptoms were 64% vs. 35%.
The intervention also was effective at preventing depression among 137 patients without depressive symptoms at baseline. In this group, 13% of patients who received the CALM intervention had depressive symptoms at 3 months, compared with 30% of controls.
In addition, patients who received CALM support at both 3 and 6 months said they were better prepared for the end of life, reported that they had greater opportunity to talk about their concerns for the future, were less frightened, and said they had greater ability to express and manage their feelings. At 6 months these effects were strengthened, and the CALM group also felt more able to understand their cancer experience, deal with changes in relationships as a result of cancer, explore ways of communicating with their health care team and family, and clarify their values and beliefs.
“The intervention addresses both the practical problems that people face, and there are many – How do I manage my pain? My symptoms? – but also the profound problems and issues that people face – What is the meaning of my life? – when having a terminal diagnosis, for instance,” he said.
The investigators are currently establishing a global network to train health professionals in the delivery of CALM, and to evaluate the program’s effectiveness in different clinical settings and cultures, he said.
The STREAM study was institutionally supported. Dr. Hess disclosed travel and accommodations from CSL Behring. The Conquer Fear study was funded by Cancer Australia, beyondBlue, and the Australian National Breast Cancer Foundation. Dr. Beith reported no relevant disclosures. The CALM study was supported by the Canadian Institute of Health Research. Dr. Rodin reported no relevant disclosures.
AT ASCO 2017
Key clinical point: Oncologists and patients may focus on only the clinical aspects of care while overlooking cancer-associated distress, anxiety, or fear.
Major finding: Each of three psychological interventions was effective at reducing mental health symptoms in patients with cancer.
Data source: Randomized trials of interventions aimed at relieving mental health symptoms associated with a new cancer diagnoses, fear of cancer recurrence, and advanced or metastatic disease.
Disclosures: The STREAM study was institutionally supported. Dr. Hess disclosed travel and accommodations from CSL Behring. The Conquer Fear study was funded by Cancer Australia, beyondBlue, and the Australian National Breast Cancer Foundation. Dr. Beith reported no relevant disclosures. The CALM study was supported by the Canadian Institute of Health Research. Dr. Rodin reported no relevant disclosures.
VIDEO: TRK inhibitor shows 76% ORR across diverse cancers harboring TRK fusions
CHICAGO – An integrated analysis of three trials has shown that larotrectinib, an oral selective inhibitor of tropomyosin receptor kinase (TRK), has durable efficacy across diverse adult and pediatric cancers harboring TRK fusions, netting an impressive 76% overall response rate.
Lead study author David Hyman, MD, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York, discussed highlights of the analysis, larotrectinib’s regulatory status, and implications for TRK fusion testing in clinical care at the annual meeting of the American Society of Clinical Oncology.
Dr. Hyman disclosed that he has a consulting or advisory role with Atara Biotherapeutics, Chugai Pharma, and CytomX Therapeutics, and that he receives research funding from AstraZeneca and Puma Biotechnology. The study was funded by Loxo Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – An integrated analysis of three trials has shown that larotrectinib, an oral selective inhibitor of tropomyosin receptor kinase (TRK), has durable efficacy across diverse adult and pediatric cancers harboring TRK fusions, netting an impressive 76% overall response rate.
Lead study author David Hyman, MD, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York, discussed highlights of the analysis, larotrectinib’s regulatory status, and implications for TRK fusion testing in clinical care at the annual meeting of the American Society of Clinical Oncology.
Dr. Hyman disclosed that he has a consulting or advisory role with Atara Biotherapeutics, Chugai Pharma, and CytomX Therapeutics, and that he receives research funding from AstraZeneca and Puma Biotechnology. The study was funded by Loxo Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – An integrated analysis of three trials has shown that larotrectinib, an oral selective inhibitor of tropomyosin receptor kinase (TRK), has durable efficacy across diverse adult and pediatric cancers harboring TRK fusions, netting an impressive 76% overall response rate.
Lead study author David Hyman, MD, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York, discussed highlights of the analysis, larotrectinib’s regulatory status, and implications for TRK fusion testing in clinical care at the annual meeting of the American Society of Clinical Oncology.
Dr. Hyman disclosed that he has a consulting or advisory role with Atara Biotherapeutics, Chugai Pharma, and CytomX Therapeutics, and that he receives research funding from AstraZeneca and Puma Biotechnology. The study was funded by Loxo Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ASCO 2017
