Long-term outcomes with monotherapy
In a related presentation, Michael J. Overman, MD, an associate professor at the University of Texas MD Anderson Cancer Center, Houston, reported long-term outcomes with nivolumab monotherapy on CheckMate-142 according to prior lines of therapy.
Patients given monotherapy were classified as more heavily pretreated (at least three prior therapies, including a fluoropyrimidine, oxaliplatin, and irinotecan) and less heavily pretreated (at most two prior therapies, usually excluding irinotecan).
Dr. Michael J. Overman
“Deepening of response was shown with further follow-up,” he noted; in particular, the rate of complete response increased from 3% to 9%. “This is primarily related to partial responses that have converted to complete responses with additional time.” Median duration of response was not reached.
The overall response rate was 26% in the more heavily pretreated group and 52% in the less heavily pretreated group, although confidence intervals overlapped. The disease control rate was 55% and 81%, respectively.
Both progression-free and overall survival curves for the entire monotherapy cohort showed a plateau. The 12-month rates were 44% (also 44% at 18 months) and 72% (67% at 18 months), respectively.
The rate of grade 3 or 4 treatment-related adverse events was 20%. “No new signals were seen with this longer follow-up,” Dr. Overman noted.
“Nivolumab continued to provide durable clinical benefit with long-term follow-up in previously treated patients with dMMR/MSI-H metastatic colorectal cancer. “Durable clinical benefit with deepening of response was observed regardless of prior chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan,” he summarized. “These results support ongoing evaluation of nivolumab-based therapy in the first-line setting in patients with deficient–mismatch repair colorectal cancer.”
Findings in context
“This secondary analysis is of interest, but this is an unplanned retrospective subgroup analysis of this data,” commented Dr. Stadler, the discussant. “I think the take-home message here is that both the heavily pretreated and not-so-heavily pretreated groups have clinical benefit from this therapy. Certainly, longer-term follow-up continues to support the use of nivolumab monotherapy in previously treated dMMR colorectal cancer.”
The findings for the whole nivolumab monotherapy cohort generally mirror those seen with pembrolizumab (Keytruda), another anti–PD-1 antibody, in this patient population, except for a shorter time to response with the former, she noted. “This suggests that both nivolumab and pembrolizumab are reasonable monotherapies in metastatic MSI-H colorectal cancer.”
“Evaluation of anti–PD-1 therapies in the first-line setting is certainly warranted,” Dr. Stadler concluded. “In fact, the KEYNOTE-177 trial is a phase 3 randomized study of pembrolizumab versus investigator-choice chemotherapy for mismatch repair–deficient colorectal cancer that is already investigating this question and that is nearing completion of accrual.”
Dr. Andre disclosed that he receives honoraria from Baxter, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, MSD Oncology, Novartis, Roche/Genentech, Sanofi, Servier, and Xbiotech; that he has a consulting or advisory role with Amgen, Bristol-Myers Squibb, HalioDX, MSD Oncology, Mundipharma, Roche/Genentech, and Servier; and that he receives travel expenses from Amgen, Bristol-Myers Squibb, and Roche/Genentech. Dr. Overman disclosed that he has a consulting or advisory role with Bristol-Myers Squibb, Merrimack, and Roche/Genentech, and receives research funding Amgen, Bristol-Myers Squibb, Celgene, MedImmune, Merck, and Roche. The trial was sponsored by Bristol-Myers Squibb.
SOURCES: André T et al. GI Cancers Symposium Abstract 553, Overman MJ et al. GI Cancer Symposium Abstract 554.