For the first-line treatment of microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer, pembrolizumab is superior to chemotherapy for prolonging progression-free survival, according to a study published in the Dec. 3 issue of the New England Journal of Medicine.
Thierry André, M.D., from Sorbonne Université and Hôpital Saint Antoine in Paris, and colleagues conducted a phase 3, open-label trial involving 307 patients with metastatic MSI-H-dMMR colorectal cancer who had not previously received treatment. Participants were randomly assigned in a 1:1 ratio to receive either pembrolizumab (200 mg every three weeks) or chemotherapy every two weeks.
After a median follow-up of 32.4 months, at the second interim analysis, the researchers found that pembrolizumab was superior to chemotherapy with respect to progression-free survival (median, 16.5 versus 8.2 months; hazard ratio, 0.60). After 24 months of follow-up, the estimated restricted mean survival was 13.7 months compared with 10.8 months. Overall, 56 and 69 patients in the pembrolizumab and chemotherapy groups, respectively, had died as of the data cutoff date; data on overall survival were still evolving. An overall response was seen in 43.8 and 33.1 percent of patients in the pembrolizumab and chemotherapy groups, respectively. Among those with an overall response, 83 and 35 percent of those in the pembrolizumab and chemotherapy groups, respectively, had ongoing responses at 24 months.
“These data represent another step forward for biomarker-driven studies targeting MSI-H-dMMR colorectal cancers,” the authors write. “Pembrolizumab should be considered an option for initial therapy for patients with MSI-H-dMMR metastatic colorectal cancer.”
Several authors disclosed financial ties to pharmaceutical companies, including Merck, which manufactures pembrolizumab and partially funded the study.