{"entity":{"id":"paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020","kind":"paper","name":"KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer","aka":[],"tldr":"Pembrolizumab shrank tumours in about a third of patients with mismatch repair-deficient cancers of many different organs, with responses that often lasted years; the pancreatic cancer group responded less often than most. It is the trial behind the tissue-agnostic approval for MSI-high cancer.","summary":"Phase 2 basket study of pembrolizumab 200 mg every three weeks in 233 patients with previously treated advanced non-colorectal MSI-high or mismatch repair-deficient cancer across 27 tumour types, endometrial, gastric, cholangiocarcinoma and pancreatic cancer among the largest cohorts.\n\nThe objective response rate was about 34 percent with a median duration of response not reached, median progression-free survival 4.1 months and median overall survival 23.5 months. In the 22 patients with pancreatic cancer the response rate was about 18 percent and median overall survival about 4 months, the lowest of the major cohorts. The data supported the FDA's tissue-agnostic approval of pembrolizumab for MSI-high cancer.","asOf":"2026-09-21","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.19.02105"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31682550/"}],"tags":[],"related":[],"cancers":["msi-high-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02628067"],"people":["aurelien-marabelle","dung-le"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.02105","pmid":"31682550","authors":"Marabelle A, Le DT, Ascierto PA, et al.","paperType":"observational","findings":["Objective response about 34 percent across 27 non-colorectal tumour types; median overall survival 23.5 months.","Pancreatic cohort of 22 patients: response about 18 percent, median overall survival about 4 months."],"whatItMeans":"Every pancreatic cancer should be tested for mismatch repair deficiency because the 1 percent who have it can receive pembrolizumab, but responses in pancreatic cancer are less frequent and less durable than in other MSI-high cancers.","caveats":["Single-arm basket study; the pancreatic cohort was small and heavily pretreated.","Some patients had MSI-high status assigned by PCR or immunohistochemistry alone, and misclassification is a known problem in pancreatic cancer."],"changedPractice":true,"participants":233},"route":"/key-papers/paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020/","neighbours":{"cancer":[{"id":"msi-high-pdac","kind":"cancer","name":"Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma","route":"/cancers/msi-high-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"trial":[{"id":"nct02628067","kind":"trial","name":"Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)","route":"/trials/nct02628067/"}],"person":[{"id":"aurelien-marabelle","kind":"person","name":"Aurélien Marabelle","route":"/people/aurelien-marabelle/"},{"id":"dung-le","kind":"person","name":"Dung T. Le","route":"/people/dung-le/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}