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SAN FRANCISCO – First-line dual immune checkpoint inhibitor therapy for microsatellite instability–high/DNA mismatch repair–deficient (MSI-H/dMMR) metastatic colorectal cancer has impressive durability, an update of the multicohort CheckMate 142 trial shows.
“We all know that MSI-H colorectal cancer patients have a poor prognosis,” said lead investigator Heinz-Josef Lenz, MD, codirector of the Colorectal Center and section head of the GI oncology program at the University of Southern California Norris Comprehensive Cancer Center, Los Angeles. First-line chemotherapy in this population yields median overall survival on the order of 20-22 months.
The cohort of 45 patients treated on the phase 2 trial received the programmed death–1 inhibitor nivolumab (Opdivo) every 2 weeks, plus a low dose of the CTLA4 inhibitor ipilimumab (Yervoy) every 6 weeks as first-line therapy for MSI-H metastatic colorectal cancer. (Nivolumab, with or without ipilimumab, has received Food and Drug Administration accelerated approval as second-line therapy based on data from other cohorts in the trial.)
Previously reported initial results, at a median follow-up of 13.8 months, showed that the investigator-assessed objective response rate was 60% (ESMO 2018, Abstract LBA18_PR). As of the update, now at a median follow-up of 19.9 months, that rate was 64%, according to data reported at the 2020 GI Cancers Symposium.
“Nivolumab and ipilimumab demonstrates clinically meaningful durable benefits and may present an option for first-line treatment for MSI-H metastatic colorectal cancer patients,” Dr. Lenz summarized.
“The incredible complete response rates and overall response rates seen are never seen with chemotherapy, and it’s very well tolerated, so if I have a choice, I would start with nivolumab-ipilimumab in first-line MSI-H,” he added. “The [National Comprehensive Cancer Network] guidelines recommend that you can start in first line with this combination if patients are not candidates for chemotherapy. So they leave this door open, that you have an opportunity to use immunotherapy in this patient population.”
Choosing single or dual immunotherapy
Given the so-called financial toxicity of dual nivolumab and ipilimumab therapy and lack of a randomized comparison against single-agent nivolumab, a session attendee said, can clinicians simply use the latter?
“Very importantly, in this clinical trial, ipilimumab was given every 6 weeks. As you know, the 2-week regimens are significantly more toxic,” Dr. Lenz noted. The combination using this low dose has safety similar to that seen with nivolumab alone. And in cross-trial comparisons, at least, “the combination seems to be a little bit more active, so I always choose both,” he said, adding that the financial aspects are beyond his purview.
However, session cochair Joseph J.Y. Sung, MD, PhD, MBBS, the Mok Hing Yiu Professor of Medicine in the department of medicine and therapeutics at the Chinese University of Hong Kong, had a different view.
“I think there is still room for a randomized study to prove the combination’s superiority against single immunotherapy,” he said in an interview. “If I’m treating an MSI patient, I would stick to single immunotherapy until I see more evidence that this combination has a substantial improvement in the outcome that is worth the money.”
Study details
The patients studied were unselected for baseline tumor expression of programmed death–ligand 1, with 27% having expression of 1% or greater and 58% having expression below that threshold.
As of the data cutoff for the update, 47% of patients were still on treatment, Dr. Lenz reported at the symposium, sponsored by the American Gastroenterological Association, American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. The most common reason for stopping treatment was disease progression.
The investigator-assessed objective response rate, the primary endpoint, consisted of complete responses in 9% of patients and partial responses in 56%. (The rate as assessed by blinded independent central reviewers was 58%, consisting of complete responses in 18% and partial responses in 40%.)
“The high response rate was consistent among all evaluated subgroups,” Dr. Lenz noted, with no differences detected by presence or absence of Lynch syndrome and/or specific microsatellite-related mutations.
Median time to response was 2.6 months, and median duration of response was not reached. Median progression-free and overall survival were also not reached, but 15-month rates were 75% and 84%, respectively.
The rate of grade 3-4 treatment-related adverse events was 20%, and the rate of grade 3-4 serious treatment-related adverse events was 11%. Only 4% of patients discontinued treatment because of such events.
Ongoing trials may take immunotherapy even further in this patient population, according to Dr. Lenz. “We are all waiting for the treatments with the immunotherapy in combination with chemo and bevacizumab in first line. Will that change the efficacy and toxicity?” he elaborated. “You can imagine, in the MSI-H patients with the immunotherapy alone, we haven’t reached median progression-free and overall survival, so it may take a long time to get this data.”
Dr. Lenz reported receiving honoraria from Bayer, Boehringer Ingelheim, Merck Serono, and Roche; consulting or advising with Bayer, Merck Serono, Pfizer, and Roche; receiving travel expenses from Bayer, Merck Serono, and Roche. The trial was funded by Bristol-Myers Squibb. Dr. Sung reported that he had no relevant conflicts of interest.
SOURCE: Lenz H-J et al. 2020 GI Cancers Symposium, Abstract 11.
SAN FRANCISCO – First-line dual immune checkpoint inhibitor therapy for microsatellite instability–high/DNA mismatch repair–deficient (MSI-H/dMMR) metastatic colorectal cancer has impressive durability, an update of the multicohort CheckMate 142 trial shows.
“We all know that MSI-H colorectal cancer patients have a poor prognosis,” said lead investigator Heinz-Josef Lenz, MD, codirector of the Colorectal Center and section head of the GI oncology program at the University of Southern California Norris Comprehensive Cancer Center, Los Angeles. First-line chemotherapy in this population yields median overall survival on the order of 20-22 months.
The cohort of 45 patients treated on the phase 2 trial received the programmed death–1 inhibitor nivolumab (Opdivo) every 2 weeks, plus a low dose of the CTLA4 inhibitor ipilimumab (Yervoy) every 6 weeks as first-line therapy for MSI-H metastatic colorectal cancer. (Nivolumab, with or without ipilimumab, has received Food and Drug Administration accelerated approval as second-line therapy based on data from other cohorts in the trial.)
Previously reported initial results, at a median follow-up of 13.8 months, showed that the investigator-assessed objective response rate was 60% (ESMO 2018, Abstract LBA18_PR). As of the update, now at a median follow-up of 19.9 months, that rate was 64%, according to data reported at the 2020 GI Cancers Symposium.
“Nivolumab and ipilimumab demonstrates clinically meaningful durable benefits and may present an option for first-line treatment for MSI-H metastatic colorectal cancer patients,” Dr. Lenz summarized.
“The incredible complete response rates and overall response rates seen are never seen with chemotherapy, and it’s very well tolerated, so if I have a choice, I would start with nivolumab-ipilimumab in first-line MSI-H,” he added. “The [National Comprehensive Cancer Network] guidelines recommend that you can start in first line with this combination if patients are not candidates for chemotherapy. So they leave this door open, that you have an opportunity to use immunotherapy in this patient population.”
Choosing single or dual immunotherapy
Given the so-called financial toxicity of dual nivolumab and ipilimumab therapy and lack of a randomized comparison against single-agent nivolumab, a session attendee said, can clinicians simply use the latter?
“Very importantly, in this clinical trial, ipilimumab was given every 6 weeks. As you know, the 2-week regimens are significantly more toxic,” Dr. Lenz noted. The combination using this low dose has safety similar to that seen with nivolumab alone. And in cross-trial comparisons, at least, “the combination seems to be a little bit more active, so I always choose both,” he said, adding that the financial aspects are beyond his purview.
However, session cochair Joseph J.Y. Sung, MD, PhD, MBBS, the Mok Hing Yiu Professor of Medicine in the department of medicine and therapeutics at the Chinese University of Hong Kong, had a different view.
“I think there is still room for a randomized study to prove the combination’s superiority against single immunotherapy,” he said in an interview. “If I’m treating an MSI patient, I would stick to single immunotherapy until I see more evidence that this combination has a substantial improvement in the outcome that is worth the money.”
Study details
The patients studied were unselected for baseline tumor expression of programmed death–ligand 1, with 27% having expression of 1% or greater and 58% having expression below that threshold.
As of the data cutoff for the update, 47% of patients were still on treatment, Dr. Lenz reported at the symposium, sponsored by the American Gastroenterological Association, American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. The most common reason for stopping treatment was disease progression.
The investigator-assessed objective response rate, the primary endpoint, consisted of complete responses in 9% of patients and partial responses in 56%. (The rate as assessed by blinded independent central reviewers was 58%, consisting of complete responses in 18% and partial responses in 40%.)
“The high response rate was consistent among all evaluated subgroups,” Dr. Lenz noted, with no differences detected by presence or absence of Lynch syndrome and/or specific microsatellite-related mutations.
Median time to response was 2.6 months, and median duration of response was not reached. Median progression-free and overall survival were also not reached, but 15-month rates were 75% and 84%, respectively.
The rate of grade 3-4 treatment-related adverse events was 20%, and the rate of grade 3-4 serious treatment-related adverse events was 11%. Only 4% of patients discontinued treatment because of such events.
Ongoing trials may take immunotherapy even further in this patient population, according to Dr. Lenz. “We are all waiting for the treatments with the immunotherapy in combination with chemo and bevacizumab in first line. Will that change the efficacy and toxicity?” he elaborated. “You can imagine, in the MSI-H patients with the immunotherapy alone, we haven’t reached median progression-free and overall survival, so it may take a long time to get this data.”
Dr. Lenz reported receiving honoraria from Bayer, Boehringer Ingelheim, Merck Serono, and Roche; consulting or advising with Bayer, Merck Serono, Pfizer, and Roche; receiving travel expenses from Bayer, Merck Serono, and Roche. The trial was funded by Bristol-Myers Squibb. Dr. Sung reported that he had no relevant conflicts of interest.
SOURCE: Lenz H-J et al. 2020 GI Cancers Symposium, Abstract 11.
SAN FRANCISCO – First-line dual immune checkpoint inhibitor therapy for microsatellite instability–high/DNA mismatch repair–deficient (MSI-H/dMMR) metastatic colorectal cancer has impressive durability, an update of the multicohort CheckMate 142 trial shows.
“We all know that MSI-H colorectal cancer patients have a poor prognosis,” said lead investigator Heinz-Josef Lenz, MD, codirector of the Colorectal Center and section head of the GI oncology program at the University of Southern California Norris Comprehensive Cancer Center, Los Angeles. First-line chemotherapy in this population yields median overall survival on the order of 20-22 months.
The cohort of 45 patients treated on the phase 2 trial received the programmed death–1 inhibitor nivolumab (Opdivo) every 2 weeks, plus a low dose of the CTLA4 inhibitor ipilimumab (Yervoy) every 6 weeks as first-line therapy for MSI-H metastatic colorectal cancer. (Nivolumab, with or without ipilimumab, has received Food and Drug Administration accelerated approval as second-line therapy based on data from other cohorts in the trial.)
Previously reported initial results, at a median follow-up of 13.8 months, showed that the investigator-assessed objective response rate was 60% (ESMO 2018, Abstract LBA18_PR). As of the update, now at a median follow-up of 19.9 months, that rate was 64%, according to data reported at the 2020 GI Cancers Symposium.
“Nivolumab and ipilimumab demonstrates clinically meaningful durable benefits and may present an option for first-line treatment for MSI-H metastatic colorectal cancer patients,” Dr. Lenz summarized.
“The incredible complete response rates and overall response rates seen are never seen with chemotherapy, and it’s very well tolerated, so if I have a choice, I would start with nivolumab-ipilimumab in first-line MSI-H,” he added. “The [National Comprehensive Cancer Network] guidelines recommend that you can start in first line with this combination if patients are not candidates for chemotherapy. So they leave this door open, that you have an opportunity to use immunotherapy in this patient population.”
Choosing single or dual immunotherapy
Given the so-called financial toxicity of dual nivolumab and ipilimumab therapy and lack of a randomized comparison against single-agent nivolumab, a session attendee said, can clinicians simply use the latter?
“Very importantly, in this clinical trial, ipilimumab was given every 6 weeks. As you know, the 2-week regimens are significantly more toxic,” Dr. Lenz noted. The combination using this low dose has safety similar to that seen with nivolumab alone. And in cross-trial comparisons, at least, “the combination seems to be a little bit more active, so I always choose both,” he said, adding that the financial aspects are beyond his purview.
However, session cochair Joseph J.Y. Sung, MD, PhD, MBBS, the Mok Hing Yiu Professor of Medicine in the department of medicine and therapeutics at the Chinese University of Hong Kong, had a different view.
“I think there is still room for a randomized study to prove the combination’s superiority against single immunotherapy,” he said in an interview. “If I’m treating an MSI patient, I would stick to single immunotherapy until I see more evidence that this combination has a substantial improvement in the outcome that is worth the money.”
Study details
The patients studied were unselected for baseline tumor expression of programmed death–ligand 1, with 27% having expression of 1% or greater and 58% having expression below that threshold.
As of the data cutoff for the update, 47% of patients were still on treatment, Dr. Lenz reported at the symposium, sponsored by the American Gastroenterological Association, American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. The most common reason for stopping treatment was disease progression.
The investigator-assessed objective response rate, the primary endpoint, consisted of complete responses in 9% of patients and partial responses in 56%. (The rate as assessed by blinded independent central reviewers was 58%, consisting of complete responses in 18% and partial responses in 40%.)
“The high response rate was consistent among all evaluated subgroups,” Dr. Lenz noted, with no differences detected by presence or absence of Lynch syndrome and/or specific microsatellite-related mutations.
Median time to response was 2.6 months, and median duration of response was not reached. Median progression-free and overall survival were also not reached, but 15-month rates were 75% and 84%, respectively.
The rate of grade 3-4 treatment-related adverse events was 20%, and the rate of grade 3-4 serious treatment-related adverse events was 11%. Only 4% of patients discontinued treatment because of such events.
Ongoing trials may take immunotherapy even further in this patient population, according to Dr. Lenz. “We are all waiting for the treatments with the immunotherapy in combination with chemo and bevacizumab in first line. Will that change the efficacy and toxicity?” he elaborated. “You can imagine, in the MSI-H patients with the immunotherapy alone, we haven’t reached median progression-free and overall survival, so it may take a long time to get this data.”
Dr. Lenz reported receiving honoraria from Bayer, Boehringer Ingelheim, Merck Serono, and Roche; consulting or advising with Bayer, Merck Serono, Pfizer, and Roche; receiving travel expenses from Bayer, Merck Serono, and Roche. The trial was funded by Bristol-Myers Squibb. Dr. Sung reported that he had no relevant conflicts of interest.
SOURCE: Lenz H-J et al. 2020 GI Cancers Symposium, Abstract 11.
REPORTING FROM THE 2020 GI CANCERS SYMPOSIUM