Overall survival analysis of KEYNOTE-177: pembrolizumab versus chemotherapy for MSI-H/dMMR mCRC

The multinational phase 3 KEYNOTE-177 study randomized patients with previously untreated MSI-H/dMMR metastatic colorectal cancer to pembrolizumab or chemotherapy, with the option of crossover to pembrolizumab after progression in the chemotherapy group. Final analysis of the study after median 44.5 months follow-up found median overall survival not reached with pembrolizumab versus 36.7 months with chemotherapy (HR 0.74; p=0.036). Superiority of pembrolizumab versus chemotherapy for overall survival was not demonstrated because the prespecified α of 0.025 was not achieved. Grade 3 or higher TRAEs were reported for 22% of patients with pembrolizumab versus 66% with chemotherapy, including one grade 5 TRAE in the chemotherapy group (intestinal perforation). The authors conclude that the findings support pembrolizumab as an efficacious first-line therapy in patients with MSI-H/dMMR mCRC.