Multinational phase 2 study of pembrolizumab for MSI-H/dMMR advanced solid tumors: updated results of KEYNOTE-158

Genomes of tumors that are deficient in DNA mismatch repair (dMMR) have high microsatellite instability (MSI-H) and are likely to be immunogenic, triggering upregulation of immune checkpoint proteins. The multinational phase 2 KEYNOTE-158 trial evaluates pembrolizumab (200 mg once every 3 weeks for 2 years or until progression or toxicity) for MSI-H/dMMR advanced noncolorectal solid tumors. Updated results after median 4.5 years of follow-up have now been published. The primary endpoint of overall response rate was 33.8%. Median duration of response was 63.2 months, median progression-free survival was 4.0 months, and median overall survival was 19.8 months. Grade ≥ 3 treatment-related adverse events occurred in 13% of patients. The authors conclude that these results further support pembrolizumab use in MSI-H/dMMR tumors.