Clinical Benefits of First-line Pembrolizumab in MSI-H–dMMR Metastatic Colorectal Cancer¹

Programmed death 1 (PD-1) blockade has been reported to be beneficial in microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) tumours after first-line treatment. Recently, the efficacy of pembrolizumab, a PD-1 inhibitor, as first-line therapy for MSI-H-dMMR advanced or metastatic colorectal cancer has been examined in the KEYNOTE-177 trial. In the open-label trial, 307 patients with metastatic MSI-H-dMMR colorectal cancer who had not previously received treatment were randomly assigned to receive pembrolizumab or chemotherapy. Patients receiving chemotherapy could cross over to pembrolizumab therapy after disease progression. After a median follow-up period of 32.4 months, pembrolizumab was superior to chemotherapy with respect to progression-free survival (PFS, median: 16.5 vs. 8.2 months, hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.45 to 0.80, P=0.0002). Besides, treatment-related adverse events of grade 3 or higher was fewer in pembrolizumab group (22%) as compared with the chemotherapy group (66%). While data on overall survival (OS) were still evolving, first-line pembrolizumab yielded significantly longer PFS than chemotherapy for MSI-H-dMMR metastatic colorectal cancer, with fewer treatment-related adverse events.

References

1. André et al. N Engl J Med 2020; 383: 2207-18.