CoChat
Sign Up
Cited by 256Cancer Immunotherapy and BiomarkersColorectal Cancer Treatments and StudiesGenetic factors in colorectal cancer

The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.

Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial

André, Thierry, Elez, Elena, Lenz, Heinz-Josef, Jensen, Lars Henrik, Touchefeu, Yann, Van Cutsem, Eric, Garcia-Carbonero, Rocio, Tougeron, David, Mendez, Guillermo Ariel, Schenker, Michael, de la Fouchardiere, Christelle, Limon, Maria Luisa, Yoshino, Takayuki, Li, Jin, Manzano Mozo, Jose Luis, Dahan, Laetitia, Tortora, Giampaolo, Chalabi, Myriam, Goekkurt, Eray, Braghiroli, Maria Ignez, Joshi, Rohit, Cil, Timucin, Aubin, Francine, Cela, Elvis, Chen, Tian, Lei, Ming, Jin, Lixian, Blum, Steven I, Lonardi, Sara·2025·The Lancet
DOI 10.1016/s0140-6736(24)02848-4
Open this paper in CoChat — free account

Abstract

Background CheckMate 8HW prespecified dual primary endpoints, assessed in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient status: progression-free survival with nivolumab plus ipilimumab compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab compared with nivolumab alone, regardless of previous systemic treatment for metastatic disease. In our previous report, nivolumab plus ipilimumab showed superior progression-free survival versus chemotherapy in first-line microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer in the CheckMate 8HW trial. Here, we report results from the prespecified interim analysis for the other primary endpoint of progression-free survival for nivolumab plus ipilimumab versus nivolumab across all treatment lines.Methods CheckMate 8HW is a randomised, open-label, international, phase 3 trial at 128 hospitals and cancer centres across 23 countries. Immunotherapy-naive adults with unresectable or metastatic colorectal cancer across different lines of therapy and microsatellite instability-high or mismatch repair-deficient status per local testing were randomly assigned (2:2:1) to nivolumab plus ipilimumab (nivolumab 240 mg, ipilimumab 1 mg/kg, every 3 weeks for four doses; then nivolumab 480 mg every 4 weeks; all intravenously), nivolumab (240 mg every 2 weeks for six doses, then 480 mg every 4 weeks; all intravenously), or chemotherapy with or without targeted therapies. The dual independent primary endpoints were progression-free survival by blinded independent central review with nivolumab plus ipilimumab versus chemotherapy (first line) and progression-free survival by blinded independent central review with nivolumab plus ipilimumab versus nivolumab (all lines) in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. This study is registered with ClinicalTrials.gov (NCT04008030).Findings Between Aug 16, 2019, and April 10, 2023, 707 patients were randomly assigned to nivolumab plus ipilimumab (n=354) or nivolumab alone (n=353). 296 (84%) of 354 patients in the nivolumab plus ipilimumab group and 286 (81%) of 353 patients in the nivolumab group were centrally confirmed to have microsatellite instability-high or mismatch repair-deficient status. At the data cutoff on Aug 28, 2024, median follow-up (from randomisation to data cutoff) was 47·0 months (IQR 38·4 to 53·2). Nivolumab plus ipilimumab treatment showed significant and clinically meaningful improvement in progression-free survival versus nivolumab (hazard ratio 0·62, 95% CI 0·48-0·81; p=0·0003). Median progression-free survival was not reached with nivolumab plus ipilimumab (95% CI 53·8 to not estimable) and was 39·3 months with nivolumab (22·1 to not estimable). Treatment-related adverse events of any grade occurred in 285 (81%) of 352 patients receiving nivolumab plus ipilimumab and in 249 (71%) of 351 patients receiving nivolumab; grade 3 or 4 treatment-related adverse events occurred in 78 (22%) and 50 (14%) patients, respectively. There were three treatment-related deaths: one event of myocarditis and pneumonitis each in the nivolumab plus ipilimumab group and one pneumonitis event in the nivolumab group.Interpretation Nivolumab plus ipilimumab showed superior progression-free survival versus nivolumab across all treatment lines, with a manageable safety profile, in patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. These results, together with the first-line results of superior progression-free survival with nivolumab plus ipilimumab versus chemotherapy, suggest nivolumab plus ipilimumab as a potential new standard of care for patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer.Funding Bristol Myers Squibb and Ono Pharmaceutical.

Overview

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(24)02848-4

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 22 references

Cited by

Sorted by citations

Related

See all

Metadata

Authors
André, T., Elez, E., Lenz, H.-J., Jensen, L. H., Touchefeu, Y., Van Cutsem, E., Garcia-Carbonero, R., Tougeron, D., Mendez, G. A., Schenker, M., de la Fouchardiere, C., Limon, M. L., Yoshino, T., Li, J., Manzano Mozo, J. L., Dahan, L., Tortora, G., Chalabi, M., Goekkurt, E., Braghiroli, M. I., Joshi, R., Cil, T., Aubin, F., Cela, E., Chen, T., Lei, M., Jin, L., Blum, S. I., & Lonardi, S.
Affiliations
  • Sorbonne Université (FR)
  • USC Norris Comprehensive Cancer Center (US)
  • Vejle Sygehus (DK)
  • Centre Hospitalier Universitaire de Nantes (FR)
  • Centre Hospitalier Universitaire de Poitiers (FR)
  • Fundacion Favaloro Hospital Universitario (AR)
  • University of Medicine and Pharmacy of Craiova (RO)
  • National Cancer Center Hospital East (JP)
  • Shanghai East Hospital (CN)
  • Agostino Gemelli University Polyclinic (IT)
  • The Netherlands Cancer Institute (NL)
  • University Cancer Center Hamburg (DE)
  • Universidade de São Paulo (BR)
  • Centre Hospitalier de l’Université de Montréal (CA)
  • Bristol-Myers Squibb (United States) (US)
  • Istituto Oncologico Veneto (IT)
Corresponding author
André, Thierry
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2025-02
Volume
405
Issue
10476
Pages
383-395
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(24)02848-4
OpenAlex
W4406818361
Cited by
256
References
22
Citations by year
2026: 155 · 2025: 101
FWCI
106.01
Type
journal article
Language
en
Update notices
erratum (2025-03-01)
Open access
closed
Licence
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
Funders
  • Ono Pharmaceutical Co Ltd
  • Bristol-Myers Squibb Company
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
metastatic colorectal cancer, microsatellite instability-high, mismatch repair deficiency, nivolumab, ipilimumab, immune checkpoint inhibitors, combination immunotherapy, progression-free survival, first-line therapy, chemotherapy, treatment lines, interim analysis, predictive biomarkers, PD-L1 expression, tumor-infiltrating lymphocytes, tumor mutational burden, PD-1/PD-L1 blockade
MeSH terms
Antineoplastic Agents, Immunological, Ipilimumab, Nivolumab, Progression-Free Survival, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Male, Middle Aged, Colorectal Neoplasms, Microsatellite Instability, DNA Mismatch Repair

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review