Nivolumab + ipilimumab (PD-1 + CTLA-4) improves long-term treatment-free survival vs nivolumab in MSI-H/dMMR mCRC

Nivolumab + ipilimumab (NIVO + IPI), a dual immune checkpoint regimen targeting PD-1 and CTLA-4, was compared with nivolumab (PD-1) monotherapy in the Phase 3 CheckMate 8HW trial in metastatic colorectal cancer with locally tested MSI-H/dMMR (centrally confirmed in 84% vs 81% of randomized patients; median follow-up 55.1 months; NCT04008030). Disease control was numerically higher with NIVO + IPI vs NIVO in 1L (85% vs 81%) and across all lines (84% vs 76%); subgroup medians favored NIVO + IPI for PFS in patients with SD in 1L (33.1 vs 9.2 months; HR 0.52) and in all lines regardless of metastatic burden (1 site: mPFS NR vs 60.8 months; HR 0.51; ≥2 sites: 59.2 vs 23.0 months; HR 0.70), with OS benefits emerging in key subgroups (e.g., SD: mOS NR vs 26.8 months; HR 0.43) and disease-specific OS HR 0.47. Post-treatment “functional cure” signals were more frequent with NIVO + IPI: 82% (185/226) were alive and treatment-free vs 67% (125/186) on NIVO, and 90% vs 79% were alive and systemic-treatment–free—positioning the combo as a higher-intensity alternative to PD-1 monotherapy benchmarks like 1L pembrolizumab (KEYNOTE-177 mPFS 16.5 vs 8.2 months vs chemo; OS not statistically significant at final analysis).