In phase II multicohort KEYNOTE-158 research, pembrolizumab showed persistent anticancer efficacy in 233 patients with previously treated advanced solid tumors that had mismatch repair deficient (dMMR) or microsatellite instability high (MSI-H). For a study, researchers sought tp present safety and effectiveness results for a larger group of patients with advanced MSI-H/dMMR noncolorectal malignancies who had previously received treatment and were enrolled in cohort K of the KEYNOTE-158 investigation.
Pembrolizumab 200 mg Q3W for 35 cycles or until disease progression or intolerable toxicity was administered to eligible patients with previously treated advanced noncolorectal MSI-H/dMMR solid tumors, measurable disease as per RECIST v1.1, and Eastern Cooperative Oncology Group performance status of 0 or 1. The main outcome was the objective response rate (ORR) according to RECIST v1.1 by independent central radiologic evaluation.
In KEYNOTE-158 cohort K, 351 patients with a variety of tumor types were included. Endometrial (22.5%), gastric (14.5%), and small intestine (7.4%) tumors were the most prevalent. On average, it took 37.5 (range, 0.2-55.6 months) from the first dose to the database’s cutoff date (5 October 2020). The ORR was 30.8% (95% CI 25.8% to 36.2%) among 321 patients in the efficacy population (patients who received more or around 1 dose of pembrolizumab and recruited more or equal to 6 months before the data cut-off date). The median response time was 47.5 months, with a range of 2.1+ to 51.1+ months (where “+” denotes the absence of progressing illness at the time of the most recent disease evaluation). The median overall survival was 20.1 months (95% CI 14.1-27.1 months), and the median progression-free survival was 3.5 months (95% CI 2.3-4.2 months). In 227 individuals (64.7%), there were treatment-related adverse events (AEs). About 39 patients (11.1%) experienced adverse events (AEs) related to the therapy in grades 3 to 4, and 3 (0.9%) experienced grade 5 AEs (myocarditis, pneumonia, and Guillain-Barre syndrome, n=1 each).
With a high ORR of 30.8%, lengthy median duration of response of 47.5 months, and tolerable safety across a spectrum of extensively pretreated, advanced MSI-H/dMMR noncolorectal malignancies, pembrolizumab displayed clinically relevant and lasting benefit, supporting its usage in the situation.