The Food and Drug Administration (FDA) has approved Keytruda (pembrolizumab; Merck), a programmed death receptor-1 (PD-1)-blocking antibody, as monotherapy for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. 

The approval was based on data from the open-label, active-controlled phase 3 KEYNOTE-177 trial that evaluated the efficacy and safety of pembrolizumab in 307 adult patients with MSI-H or dMMR colorectal cancer. Patients were randomized 1:1 to receive pembrolizumab 200mg intravenously (IV) every 3 weeks or an investigator’s choice of either mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) or FOLFIRI (irinotecan, leucovorin, and fluorouracil) IV every 2 weeks, with or without bevacizumab or cetuximab. The primary end point of the study was progression free survival (PFS) and overall survival (OS); overall response rate (ORR) and duration of response (DoR) were additional efficacy outcome measures.

Results showed a statistically significant improvement in PFS with pembrolizumab compared with chemotherapy (hazard ratio [HR] 0.60; 95% CI, 0.45-0.80; P =.0004); median PFS was 16.5 months (95% CI, 5.4-32.4) in the pembrolizumab arm vs 8.2 months (95% CI, 6.1-10.2) in the chemotherapy group. The OS data were not mature at the time of PFS analysis.

The ORR in the pembrolizumab group was 44% (95% CI, 35.8-52.0) compared with 33% (95% CI, 25.8-41.1) for chemotherapy. Findings also showed the median DoR was not reached with pembrolizumab compared with 10.6 month with chemotherapy. Among the 67 responders in the pembrolizumab arm, 75% had responses ≥12 months (vs 37% of the 51 responders in the chemotherapy arm) and 43% had responses ≥24 months (vs 18% for chemotherapy). 


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“Patients with unresectable or metastatic MSI-H colorectal cancer have historically faced poor outcomes, and until today, chemotherapy-containing regimens were the only FDA-approved first-line treatment options,” said Luis A. Diaz, MD, head of the division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center. “This approval helps address the unmet need to provide a new monotherapy treatment option for patients.”

A dosing regimen of 400mg every 6 weeks was also recently approved across all adult indications for Keytruda. The new dosing schedule is in addition to the approved dosage of 200mg every 3 weeks.

For more information visit keytruda.com.

This article originally appeared on MPR