KEYNOTE-177 5-Year Follow-Up Shows Durability of Pembrolizumab for mCRC

The phase 3 KEYNOTE-177 study compared the efficacy of pembrolizumab with chemotherapy for the treatment of patients with microsatellite instability-high or mismatch-repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).

The study established pembrolizumab as a first-line standard of care treatment for this patient population, providing a significant improvement in progression-free survival (PFS) over chemotherapy.

New results from a 5-year follow-up of the study have been published, offering data on the lasting durability of pembrolizumab for MSI-H/dMMR mCRC.

The study involved 307 patients who were randomized 1:1 to receive pembrolizumab 200 mg intravenously every 3 weeks (n=153) or chemotherapy (n=154). Patients assigned to chemotherapy treatment were able to cross over to pembrolizumab after centrally confirmed progressive disease.

The primary endpoints were PFS and overall survival (OS), while secondary endpoints included duration of response (DOR) and safety.

Upon data cutoff, the median follow-up was 73.3 months (64.9-89.2). A total of 57 (37%) patients who were assigned to receive chemotherapy had crossed over to pembrolizumab per protocol, and 39 (25.3%) patients received a PD-(L)1 inhibitor off protocol (effective crossover rate, 62%).

The median OS was 77.5 months in the pembrolizumab arm, and 36.7 months in the chemotherapy arm (HR, 0.73; 95% CI, 0.53-0.99), while the 5-year OS rates were 54.8% versus 44.2%, respectively.

The median PFS was 16.5 months with pembrolizumab and 8.2 months with chemotherapy (HR, 0.60; 95% CI, 0.45-0.79), and the median DOR was 75.4 months (range, 2.3+ to 80.1+) with pembrolizumab versus 10.6 months (range, 2.8 to 71.5+) with chemotherapy.

Fewer patients in the pembrolizumab arm experienced adverse events compared with the chemotherapy arm (80% vs 99%; grade 3-5, 22% versus 67%).

This >5 year follow-up shows the consistent durability of treatment with pembrolizumab for MSI-H/dMMR mCRC, cementing its status as a standard of care for this disease state.