Nivolumab Plus Ipilimumab Prolonged Progression-Free Survival for Patients with MSI-H/dMMR Metastatic Colorectal Cancer
Interim analysis results from the phase 3 CheckMate 8HW trial demonstrated that nivolumab plus ipilimumab prolonged progression-free survival (PFS) compared to chemotherapy alone among patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer.
According to Thierry Andre, MD, Saint Antoine Hospital, Paris, France, and coauthors, patients generally “have poor outcomes with standard chemotherapy with or without targeted therapies [however] nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies.”
In this open-label study, researchers enrolled patients with unresectable, MSI-H or dMMR metastatic colorectal cancer. Patients were randomized on a 2-to-2-to-1 basis to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy alone. The dual primary end points were PFS in the nivolumab plus ipilimumab arm compared to the chemotherapy arm in the first-line setting and PFS in the nivolumab plus ipilimumab arm compared with the nivolumab alone arm regardless of previous systemic treatment for metastatic disease. In this analysis, the PFS comparing nivolumab plus ipilimumab to chemotherapy was assessed.
At a median follow-up of 31.5 months, the 24-month PFS rate was 72% in the nivolumab plus ipilimumab arm and 14% in the chemotherapy arm (P < .001). Restricted mean survival time was 10.6 months longer in the nivolumab plus ipilimumab arm. Grade 3/4 treatment-related adverse events occurred in 23% of patients in the nivolumab plus ipilimumab arm and 48% of patients in the chemotherapy arm.
As Dr Andre et al concluded, “Progression-free survival was longer with nivolumab plus ipilimumab than with chemotherapy among patients who had not previously received systemic treatment for MSI-H or dMMR metastatic colorectal cancer.”
Source:
Andre T, Elez E, Van Cutsem EV, et al. Nivolumab plus ipilimumab in microsatellite-instability–high metastatic colorectal cancer. N Engl J Med. Published online: November 27, 2024. Doi: 10.1056/NEJMoa2402141
