{"entity":{"id":"paper-andre-keynote-177-pembrolizumab-msi-high-nejm-2020","kind":"paper","name":"Pembrolizumab in microsatellite-instability-high advanced colorectal cancer (KEYNOTE-177)","aka":[],"tldr":"The randomised trial that replaced chemotherapy with a single antibody as the first treatment for the 5 percent of metastatic bowel cancers with a broken DNA spell-checker: 16.5 against 8.2 months without progression, and a quarter of the severe side effects.","summary":"André, Shiu, Kim and colleagues randomly assigned 307 patients with previously untreated metastatic microsatellite-instability-high or mismatch repair-deficient colorectal cancer 1:1 to pembrolizumab 200 mg every three weeks or to fluorouracil-based chemotherapy with or without bevacizumab or cetuximab every two weeks, with crossover to pembrolizumab permitted after progression on chemotherapy. The two primary end points were progression-free survival and overall survival.\n\nAmong patients with an overall response, 83 percent in the pembrolizumab group against 35 percent in the chemotherapy group had ongoing responses at 24 months, which is the durability that distinguishes checkpoint blockade from chemotherapy in this population.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa2017699"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33264544/"},{"label":"Five-year follow-up (Ann Oncol 2024)","url":"https://www.annalsofoncology.org/article/S0923-7534(24)04949-4/fulltext"}],"tags":["colorectal-evidence"],"related":["paper-le-pd1-blockade-mismatch-repair-deficiency-nejm-2015","paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024"],"cancers":["colorectal","msi-high-colorectal"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["msi","mmr"],"trials":["keynote-177"],"people":["thierry-andre","eric-van-cutsem","yoshino-takayuki","luis-diaz"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2017699","pmid":"33264544","authors":"André T, Shiu KK, Kim TW, et al.","paperType":"rct","findings":["At a median 32.4 months, median progression-free survival 16.5 against 8.2 months: hazard ratio 0.60 (95 percent CI 0.45 to 0.80, p=0.0002).","Overall response 43.8 percent with pembrolizumab against 33.1 percent with chemotherapy.","Ongoing responses at 24 months in 83 percent against 35 percent of responders.","Treatment-related adverse events of grade 3 or higher in 22 percent against 66 percent, including one death in the chemotherapy group."],"whatItMeans":"First-line chemotherapy-free treatment for mismatch repair-deficient metastatic colorectal cancer, approved in June 2020; the five-year follow-up published in 2024 reported median overall survival of 77.5 months despite 62 percent crossover.","caveats":["Overall survival data were immature at this report and were confounded by 62 percent crossover from chemotherapy.","Around 30 percent of patients progressed within the first six months on pembrolizumab, and the combination trials (CheckMate 8HW) address that group.","Local rather than central mismatch repair testing determined eligibility."],"changedPractice":true,"participants":307},"route":"/key-papers/paper-andre-keynote-177-pembrolizumab-msi-high-nejm-2020/","neighbours":{"paper":[{"id":"paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024","kind":"paper","name":"Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer (CheckMate 8HW)","route":"/key-papers/paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024/"},{"id":"paper-le-pd1-blockade-mismatch-repair-deficiency-nejm-2015","kind":"paper","name":"PD-1 blockade in tumors with mismatch-repair deficiency","route":"/key-papers/paper-le-pd1-blockade-mismatch-repair-deficiency-nejm-2015/"}],"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":"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":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"}],"trial":[{"id":"keynote-177","kind":"trial","name":"KEYNOTE-177","route":"/trials/keynote-177/"}],"person":[{"id":"eric-van-cutsem","kind":"person","name":"Eric Van Cutsem","route":"/people/eric-van-cutsem/"},{"id":"luis-diaz","kind":"person","name":"Luis A. Diaz Jr.","route":"/people/luis-diaz/"},{"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/"}]}}