{"entity":{"id":"paper-antonarakis-keynote-199-pembrolizumab-jco-2020","kind":"paper","name":"KEYNOTE-199: pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer","aka":["KEYNOTE-199","Antonarakis 2020 pembrolizumab prostate"],"tldr":"Checkpoint immunotherapy transformed several cancers and did almost nothing here. In 258 men with advanced prostate cancer, about 1 in 20 had a response, and whether the tumour expressed PD-L1 made no difference.","summary":"Emmanuel Antonarakis, Johann de Bono and the KEYNOTE-199 investigators gave pembrolizumab 200 mg every three weeks to 258 men with metastatic castration-resistant prostate cancer who had already had docetaxel and at least one targeted endocrine therapy, in three parallel cohorts: measurable PD-L1-positive disease, measurable PD-L1-negative disease, and bone-predominant disease irrespective of PD-L1.\n\nThe response rates, 5 percent and 3 percent in the two measurable cohorts, are the clearest statement available of why prostate cancer is called an immunologically cold tumour, and they sit consistently with the genomics: a median tumour mutational burden of 2.6 mutations per megabase and only 4 percent mismatch repair deficiency (paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019). The responses that did occur were durable, which is why the field keeps returning to the question with combinations rather than abandoning it.","asOf":"2026-09-25","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.19.01638"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31774688/"},{"label":"ClinicalTrials.gov NCT02787005","url":"https://clinicaltrials.gov/study/NCT02787005"}],"tags":["prostate-evidence"],"related":["paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","paper-kantoff-n-engl-j-med","paper-nct02861573-eur-urol-2022","paper-nct04446117-lancet-oncol-2025","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","docetaxel"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["tmb","msi"],"trials":[],"people":["johann-de-bono"],"bottlenecks":["b-immunotherapy-response","b-tme-immunosuppression","b-biomarker-validation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.19.01638","pmid":"31774688","authors":"Antonarakis ES, Piulats JM, Gross-Goupil M, et al.","paperType":"rct","findings":["Objective response rate 5 percent (95 percent confidence interval 2 to 11) in cohort 1 (measurable, PD-L1-positive, 133 patients) and 3 percent (less than 1 to 11) in cohort 2 (measurable, PD-L1-negative, 66 patients).","Median duration of response was not reached in cohort 1 (range 1.9 to at least 21.8 months) and was 10.6 months in cohort 2 (range 4.4 to 16.8 months).","Disease control rate 10 percent in cohort 1, 9 percent in cohort 2 and 22 percent in cohort 3 (bone-predominant disease, 59 patients).","Median overall survival 9.5 months in cohort 1, 7.9 months in cohort 2 and 14.1 months in cohort 3.","Treatment-related adverse events occurred in 60 percent of patients, were grade 3 to 5 in 15 percent and led to treatment discontinuation in 5 percent."],"whatItMeans":"The measured size of the immunotherapy problem in prostate cancer: a response rate in the low single figures, no signal from PD-L1 expression, and durable benefit in a small subgroup nobody can yet identify prospectively. Any claim that immunotherapy is coming to prostate cancer has to explain this trial.","caveats":["Single-arm phase 2 with no control, in a heavily pre-treated population, so the survival figures reflect prognosis as much as treatment.","PD-L1 positivity did not separate responders from non-responders, so it is not a usable biomarker here.","Mismatch repair status, which does predict response to checkpoint blockade in prostate cancer as elsewhere, was not the selection criterion; the responders in cohort 3 in particular remain unexplained."],"changedPractice":false,"participants":258},"route":"/key-papers/paper-antonarakis-keynote-199-pembrolizumab-jco-2020/","neighbours":{"paper":[{"id":"paper-nct04446117-lancet-oncol-2025","kind":"paper","name":"Cabozantinib plus atezolizumab in metastatic prostate cancer (CONTACT-02): final analyses from a phase 3, open-label, randomised trial","route":"/key-papers/paper-nct04446117-lancet-oncol-2025/"},{"id":"paper-nct02861573-eur-urol-2022","kind":"paper","name":"Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study","route":"/key-papers/paper-nct02861573-eur-urol-2022/"},{"id":"paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","kind":"paper","name":"Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","route":"/key-papers/paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019/"},{"id":"paper-kantoff-n-engl-j-med","kind":"paper","name":"Sipuleucel-T immunotherapy for castration-resistant prostate cancer","route":"/key-papers/paper-kantoff-n-engl-j-med/"}],"roadmap":[{"id":"prostate-roadmap","kind":"roadmap","name":"Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch","route":"/roadmaps/prostate-roadmap/"}],"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"section":[{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"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/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"person":[{"id":"johann-de-bono","kind":"person","name":"Johann de Bono","route":"/people/johann-de-bono/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}