Nivolumab Provides Durable Response in dMMR/MSI-H Colorectal Cancer

Nivolumab demonstrated durable disease control and responses in patients with metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer who failed prior therapy, according to a study published in The Lancet Oncology.¹

dMMR/MSI-H colorectal cancer is associated with higher tumor neoantigen load, mutational burdens, dense immune cell infiltration, and distinct biomarkers, features that are associated with a clinical response to immune checkpoint inhibitors in other tumor types.

For the Checkmate-142 trial (ClinicalTrials.gov Identifier: NCT02060188), researchers enrolled 74 patients with previously treated dMMR/MSI-H colorectal cancer to receive nivolumab 3 mg/kg every 2 weeks.

Out of 74 patients, 23 (31.1%; 95% CI, 20.8-42.9) patients achieved an objective response as per investigator assessment at the median follow-up of 12 months.

At 12 weeks, disease control was achieved in 51 (69%; 95% CI, 57-69) patients.

Treatment related adverse events (AEs) occurred in 70% of enrolled patients, and 20% of patients experienced grade 3 or 4 AEs. The most frequently reported grade 3 or 4 AEs were increased lipase and increased amylase.

None of the 23 deaths that occurred during the study were deemed treatment-related.

Reference

1. Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Jul 19. doi: 10.1016/S1470-2045(17)30422-9 [Epub ahead of print]