On June 29, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) for the first-line treatment of patients with unresectable or metastatic microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) colorectal cancer.
Approval was based on KEYNOTE‑177, a multicenter, international, open-label, active-controlled, randomized trial that enrolled 307 patients with previously untreated, unresectable or metastatic MSI-H or dMMR colorectal cancer. Determination of MSI or MMR tumor status was made locally using polymerase chain reaction or immunohistochemistry, respectively.
Patients were randomly assigned 1:1 to receive pembrolizumab at 200 mg intravenously every 3 weeks or investigator’s choice of modified FOLFOX6 (fluorouracil [5-FU], leucovorin, and oxaliplatin) or FOLFIRI (5-FU, leucovorin, and irinotecan), with or without bevacizumab or cetuximab, given intravenously every 2 weeks. Patients randomly assigned to receive chemotherapy were offered pembrolizumab at the time of disease progression.
The main efficacy outcome measures were progression-free survival and overall survival. Median progression-free survival was 16.5 months (95% confidence interval [CI] = 5.4–32.4) in the pembrolizumab arm and 8.2 months (95% CI = 6.1–10.2) in the chemotherapy arm (hazard ratio [HR] = 0.60, 95% CI = 0.45–0.80, two-sided P = .0004). At the time of the progression-free survival analysis, the overall survival data were not mature.
The most common adverse reactions reported in ≥ 20% of patients receiving pembrolizumab as a single agent were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.
The recommended pembrolizumab dose for patients with MSI-H/dMMR colorectal cancer is 200 mg every 3 weeks or 400 mg every 6 weeks.