CheckMate 8HW
In immunotherapy-naive MSI-H/dMMR metastatic colorectal cancer, how does nivolumab plus ipilimumab compare with chemotherapy in first line and nivolumab alone across treatment lines?
Evidence snapshot updated 23 October 2026. Source links are provided below; this is an evidence summary, not a substitute for current local guidelines or individual clinical judgement.
Population and treatment
Immunotherapy-naive adults with unresectable/metastatic MSI-H or dMMR colorectal cancer; independent comparisons used centrally confirmed biomarker-positive populations.
Intervention and comparator: Nivolumab 240 mg IV plus ipilimumab 1 mg/kg every 3 weeks for 4 doses, then nivolumab 480 mg every 4 weeks; comparator nivolumab alone or chemotherapy according to the prespecified comparison.
ClinicalTrials.gov: NCT04008030 ↗
Key results
In the first-line comparison, PFS HR was 0.21 (95% CI 0.14–0.32) for nivolumab plus ipilimumab vs chemotherapy; median PFS was not reached vs 5.8 months. In the all-lines comparison, combination vs nivolumab alone gave PFS HR 0.62 (95% CI 0.48–0.81); median PFS not reached vs 39.3 months.
Hazard ratio for progression or death · First-line combination vs chemotherapy
Absolute-effect interpretation: No NNT calculated from hazard ratios or median PFS. The first-line and all-lines comparisons are distinct randomised comparisons and must not be merged into one effect estimate.
Toxicity and treatment burden
Grade 3–4 treatment-related AEs in the combination-versus-nivolumab comparison were 22% vs 14%; immune-mediated colitis, hepatitis, pneumonitis and endocrinopathies require vigilance.
Interpretation and limitations
Only applies to confirmed MSI-H/dMMR disease. The first-line chemotherapy comparison and all-lines nivolumab comparison have different populations and estimands; preserve each comparison and its endpoint separately. The FDA approved the combination for unresectable/metastatic MSI-H/dMMR CRC in April 2025.
Use endpoint definitions, follow-up, analysis population and comparator exactly as reported. Do not infer NNT from a hazard ratio or median survival. Subgroup findings should not be treated as predictive unless the trial design and interaction testing support that interpretation.
Primary source and further reading
Primary publication / authoritative source ↗
Trial registry (NCT04008030) ↗
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