# Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer

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

## TL;DR

Published report from the CheckMate 8HW trial registered as NCT04008030, in New England Journal of Medicine (2024), chosen as the most cited paper whose own text cites the registry id.

## Summary

Background: Patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer.

Methods: In this phase 3 open-label trial, we randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive, in a 2:2:1 ratio, nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. The dual primary end points, assessed in patients with centrally confirmed MSI-H or dMMR status, were progression-free survival with nivolumab plus ipilimumab as compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab as compared with nivolumab alone in patients regardless of previous systemic treatment for metastatic disease. At this prespecified interim analysis, the first primary end point (involving nivolumab plus ipilimumab vs. chemotherapy) was assessed.

Results: A total of 303 patients who had not previously received systemic treatment for metastatic disease were randomly assigned to receive nivolumab plus ipilimumab or chemotherapy; 255 patients had centrally confirmed MSI-H or dMMR tumors. At a median follow-up of 31.5 months (range, 6.1 to 48.4), progression-free survival outcomes (the primary analysis) were significantly better with nivolumab plus ipilimumab than with chemotherapy (P<0.001 for the between-group difference in progression-free survival, calculated with the use of a two-sided stratified log-rank test); 24-month progression-free survival was 72% (95% confidence interval [CI], 64 to 79) with nivolumab plus ipilimumab as compared with 14% (95% CI, 6 to 25) with chemotherapy. At 24 months, the restricted mean survival time was 10.6 months (95% CI, 8.4 to 12.9) longer with nivolumab plus ipilimumab than with chemotherapy, a finding consistent with the primary analysis of progression-free survival. Grade 3 or 4 treatment-related adverse events occurred in 23% of the patients in the nivolumab-plus-ipilimumab group and in 48% of the patients in the chemotherapy group.

Conclusions: 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. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 8HW ClinicalTrials.gov number, NCT04008030.).

Indexed on Europe PMC as PubMed record 39602630 (DOI 10.1056/nejmoa2402141). Its abstract cites the registry id NCT04008030, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: New England Journal of Medicine
- Year: 2024
- DOI: 10.1056/nejmoa2402141
- Authors: Andre T, Elez E, Van Cutsem E, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT04008030 with the most citations, so it is the natural first reading for anyone following the CheckMate 8HW trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- N Engl J Med 2024: https://doi.org/10.1056/nejmoa2402141
- PubMed: https://pubmed.ncbi.nlm.nih.gov/39602630/
- Europe PMC: https://europepmc.org/article/MED/39602630
- ClinicalTrials.gov NCT04008030: https://clinicaltrials.gov/study/NCT04008030

## Connected records

- trials: [CheckMate 8HW](https://onco.cc/trials/checkmate-8hw/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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