# Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer (CheckMate 8HW)

Source: https://onco.cc/key-papers/paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024/  
OnCo record `paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Two immunotherapy drugs together kept 72 percent of patients progression-free at two years against 14 percent on chemotherapy, the largest effect size of any first-line trial in colorectal cancer.

## Summary

André, Elez, Van Cutsem and colleagues randomly assigned patients with unresectable or metastatic colorectal cancer and locally determined microsatellite-instability-high or mismatch repair-deficient status 2:2:1 to nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. The dual primary end points, assessed in patients with centrally confirmed status, were progression-free survival with the combination against chemotherapy in the first line and against nivolumab alone regardless of previous treatment; this prespecified interim analysis reports the first.

A total of 303 previously untreated patients were randomised to the combination or chemotherapy, and 255 had centrally confirmed microsatellite-instability-high or mismatch repair-deficient tumours.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: New England Journal of Medicine
- Year: 2024
- DOI: 10.1056/NEJMoa2402141
- Authors: André T, Elez E, Van Cutsem E, et al.
- Findings: At a median 31.5 months, 24-month progression-free survival 72 percent (95 percent CI 64 to 79) with nivolumab plus ipilimumab against 14 percent (6 to 25) with chemotherapy (p<0.001).; At 24 months, restricted mean survival time was 10.6 months (8.4 to 12.9) longer with the combination.; Grade 3 or 4 treatment-related adverse events in 23 percent of the combination group against 48 percent of the chemotherapy group.
- What it means: Combination checkpoint blockade became a first-line standard for mismatch repair-deficient metastatic colorectal cancer in 2025; the later all-lines comparison against nivolumab alone showed the CTLA-4 antibody adds to the PD-1 antibody, the first phase 3 to prove that in this disease.
- Caveats: Interim analysis of the first of two primary endpoints; overall survival is not mature.; Eligibility used local testing, and 48 of 303 randomised patients did not have centrally confirmed status.; No randomised comparison against pembrolizumab, so the choice between single and dual checkpoint blockade rests on cross-trial comparison.

## Sources

- N Engl J Med 2024: https://doi.org/10.1056/NEJMoa2402141
- PubMed: https://pubmed.ncbi.nlm.nih.gov/39602630/

## Connected records

- key papers: [NICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patients](https://onco.cc/key-papers/paper-niche-2-neoadjuvant-colon-nejm-2024/), [Pembrolizumab in microsatellite-instability-high advanced colorectal cancer (KEYNOTE-177)](https://onco.cc/key-papers/paper-andre-keynote-177-pembrolizumab-msi-high-nejm-2020/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Mismatch-repair deficient (MSI-high) colorectal cancer](https://onco.cc/cancers/msi-high-colorectal/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [CTLA-4](https://onco.cc/targets/ctla4/), [Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)](https://onco.cc/targets/mmr/), [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/)
- companies: [Bristol Myers Squibb](https://onco.cc/companies/bms/)
- terms: [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/)
- trials: [CheckMate 8HW](https://onco.cc/trials/checkmate-8hw/)
- people: [Eric Van Cutsem](https://onco.cc/people/eric-van-cutsem/), [Heinz-Josef Lenz](https://onco.cc/people/heinz-josef-lenz/), [Myriam Chalabi](https://onco.cc/people/myriam-chalabi/), [Takayuki Yoshino](https://onco.cc/people/yoshino-takayuki/), [Thierry André](https://onco.cc/people/thierry-andre/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)

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