Programmed death 1 (PD-1) blockage is known to have a significant clinical benefit in patients with microsatellite instability-high (MSI-H) or mismatch–repair–deficient (dMMR) cancer after previously administered therapy. However, the efficacy of PD-1 blockade as first-line therapy for MSI-H–dMMR advanced or metastatic colorectal cancer compared with chemotherapy is unknown. This study aims to compare the efficacy of pembrolizumab, a PD-1 inhibitor, with chemotherapy for the treatment of MSI-H–dMMR colorectal cancer.
This open-label, phase 3 trial included a total of 307 patients with metastatic MSI-H–dMMR colorectal cancer. The patients were randomly assigned in a 1:1 ratio to receive pembrolizumab or chemotherapy. The primary outcomes of the study were progression-free survival and overall survival.
After a median follow-up of 32.4 months, pembrolizumab was found to be superior to chemotherapy in terms of progression-free survival. The progression-free survival with pembrolizumab was 16.5 months, compared with 8.2 months with chemotherapy. The estimated restricted mean survival after 24 months was 13.7 months with pembrolizumab and 10.8 months with chemotherapy. The data on overall survival was not clear enough to draw any conclusions.
The research concluded that pembrolizumab for MSI-H–dMMR colorectal cancer was associated with a longer progression-free and restricted mean survival compared with chemotherapy.
Ref: https://www.nejm.org/doi/full/10.1056/NEJMoa2017699
