Key clinical point: In an updated KEYNOTE-177 analysis, first-line pembrolizumab vs chemotherapy did not improve survival in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC), but improved progression-free survival (PFS) and led to fewer treatment-related adverse events (TAE).
Major finding: Pembrolizumab vs chemotherapy provided no survival benefit as the one-sided α boundary for superiority (0.025) was not met (hazard ratio [HR] 0.74; P = .036). However, it prolonged median PFS (16.5 vs 8.2 months; HR 0.59; 95% CI 0.45-0.79) and lowered the grade ≥3 TAE rate (22% vs 66%).
Study details: These are the final analysis data from the phase 3 KEYNOTE-177 trial that included 307 adult patients with previously untreated MSI-H or dMMR mCRC who were randomly assigned to receive pembrolizumab or chemotherapy.
Disclosures: Merck Sharp & Dohme (MSD; Merck subsidiary) sponsored the study. Some authors reported serving on the directorial board of, receiving institutional or clinical trial funding, advisory or consultant honoraria, or travel or accommodation expenses from various sources, including MSD. The other authors are MSD employees and Merck shareholders.
Source: Diaz LA Jr et al. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): Final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022;23(5):659-670 (Apr 12). Doi: 10.1016/S1470-2045(22)00197-8