{"entity":{"id":"paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024","kind":"paper","name":"Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer (CheckMate 8HW)","aka":[],"tldr":"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.\n\nA 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.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2402141"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39602630/"}],"tags":["colorectal-evidence"],"related":["paper-andre-keynote-177-pembrolizumab-msi-high-nejm-2020","paper-niche-2-neoadjuvant-colon-nejm-2024"],"cancers":["colorectal","msi-high-colorectal"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":["pd1","ctla4"],"drugs":["nivolumab","ipilimumab"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["msi","mmr"],"trials":["checkmate-8hw"],"people":["thierry-andre","eric-van-cutsem","heinz-josef-lenz","myriam-chalabi","yoshino-takayuki"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2402141","pmid":"39602630","authors":"André T, Elez E, Van Cutsem E, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":303},"route":"/key-papers/paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024/","neighbours":{"paper":[{"id":"paper-niche-2-neoadjuvant-colon-nejm-2024","kind":"paper","name":"NICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patients","route":"/key-papers/paper-niche-2-neoadjuvant-colon-nejm-2024/"},{"id":"paper-andre-keynote-177-pembrolizumab-msi-high-nejm-2020","kind":"paper","name":"Pembrolizumab in microsatellite-instability-high advanced colorectal cancer (KEYNOTE-177)","route":"/key-papers/paper-andre-keynote-177-pembrolizumab-msi-high-nejm-2020/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"}],"section":[{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"ctla4","kind":"target","name":"CTLA-4","route":"/targets/ctla4/"},{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"}],"trial":[{"id":"checkmate-8hw","kind":"trial","name":"CheckMate 8HW","route":"/trials/checkmate-8hw/"}],"person":[{"id":"eric-van-cutsem","kind":"person","name":"Eric Van Cutsem","route":"/people/eric-van-cutsem/"},{"id":"heinz-josef-lenz","kind":"person","name":"Heinz-Josef Lenz","route":"/people/heinz-josef-lenz/"},{"id":"myriam-chalabi","kind":"person","name":"Myriam Chalabi","route":"/people/myriam-chalabi/"},{"id":"yoshino-takayuki","kind":"person","name":"Takayuki Yoshino","route":"/people/yoshino-takayuki/"},{"id":"thierry-andre","kind":"person","name":"Thierry André","route":"/people/thierry-andre/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/colorectal-roadmap/"}]}}