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Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer.
- Source :
-
The New England journal of medicine [N Engl J Med] 2024 Nov 28; Vol. 391 (21), pp. 2014-2026. - Publication Year :
- 2024
-
Abstract
- 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.<br />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.<br />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.<br />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.).<br /> (Copyright © 2024 Massachusetts Medical Society.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Female
Humans
Male
Middle Aged
DNA Mismatch Repair
Kaplan-Meier Estimate
Microsatellite Instability
Progression-Free Survival
Young Adult
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Antineoplastic Combined Chemotherapy Protocols adverse effects
Colorectal Neoplasms drug therapy
Colorectal Neoplasms genetics
Colorectal Neoplasms pathology
Colorectal Neoplasms mortality
Ipilimumab administration & dosage
Ipilimumab adverse effects
Nivolumab administration & dosage
Nivolumab adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4406
- Volume :
- 391
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 39602630
- Full Text :
- https://doi.org/10.1056/NEJMoa2402141