{"entity":{"id":"keynote-921","kind":"trial","name":"KEYNOTE-921","aka":["KEYNOTE-921","MK-3475-921"],"tldr":"Adding pembrolizumab to chemotherapy for advanced prostate cancer did not work, and it added side effects and lung inflammation.","summary":"KEYNOTE-921 randomised 1,030 men whose metastatic castration-resistant prostate cancer had progressed after androgen deprivation and one androgen receptor pathway inhibitor to pembrolizumab or placebo with docetaxel and prednisone.\n\nAt the first interim analysis (data cutoff 27 September 2021), median radiographic progression-free survival was 8.6 months (95 percent confidence interval 8.3 to 10.2) with pembrolizumab against 8.3 months (8.2 to 8.5) with placebo, hazard ratio 0.85 (0.71 to 1.01, p=0.03), which did not meet the prespecified boundary. At the final analysis (median follow-up 22.7 months), median overall survival was 19.6 months (18.2 to 20.9) against 19.0 months (17.9 to 20.9), hazard ratio 0.92 (0.78 to 1.09, p=0.17).\n\nGrade 3 or higher treatment-related adverse events occurred in 43.2 percent with pembrolizumab and 36.6 percent with placebo. Two participants on pembrolizumab and seven on placebo died of a treatment-related adverse event. Pneumonitis was the commonest immune-mediated event, 7.0 against 3.1 percent.\n\nThe separately published patient-reported outcomes found no meaningful difference in time to pain progression, median 21.1 months against not reached, hazard ratio 1.05 (0.77 to 1.43), or in health-related quality of life. Adding the checkpoint inhibitor neither helped nor harmed how men felt; it simply did not work.","status":"negative","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT03834506","url":"https://clinicaltrials.gov/study/NCT03834506"},{"label":"KEYNOTE-921 (Journal of Clinical Oncology 2025)","url":"https://doi.org/10.1200/JCO-24-01283"},{"label":"KEYNOTE-921 patient-reported outcomes (European Urology Oncology 2026)","url":"https://doi.org/10.1016/j.euo.2025.02.015"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy"],"targets":["pd1"],"drugs":["pembrolizumab","docetaxel","prednisone"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["castration-resistance","qol-pro"],"trials":["keynote-641","keynote-991","imbassador250"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03834506","phase":"3","setting":"Metastatic castration-resistant prostate cancer progressing after androgen deprivation and one androgen receptor pathway inhibitor: pembrolizumab or placebo with docetaxel and concomitant prednisone, with dual primary endpoints of radiographic progression-free survival by blinded independent central review and overall survival","sponsor":"Merck Sharp & Dohme","result":"Median radiographic progression-free survival 8.6 against 8.3 months (hazard ratio 0.85, 95 percent confidence interval 0.71 to 1.01) and overall survival 19.6 against 19.0 months (0.92, 0.78 to 1.09); neither endpoint met.","yearReported":2025,"enrolled":1030,"enrolledBasis":"randomised","enrolledNote":"1,030 participants were randomly assigned, 515 to each arm, between 30 May 2019 and 17 June 2021.","outcomes":[{"endpoint":"Radiographic progression-free survival (median)","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab with docetaxel and prednisone","n":515,"value":8.6,"note":"Did not meet the prespecified significance boundary."},{"name":"Placebo with docetaxel and prednisone","n":515,"value":8.3}],"hr":0.85,"ci":[0.71,1.01],"p":"0.03","source":"https://doi.org/10.1200/JCO-24-01283"},{"endpoint":"Overall survival (median)","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab with docetaxel and prednisone","n":515,"value":19.6},{"name":"Placebo with docetaxel and prednisone","n":515,"value":19}],"hr":0.92,"ci":[0.78,1.09],"p":"0.17","source":"https://doi.org/10.1200/JCO-24-01283"}],"replication":"CheckMate 7DX tested nivolumab with docetaxel in the same setting; a pooled analysis of the two trials, 2,060 men, found no difference in radiographic progression-free survival (hazard ratio 0.91, 0.81 to 1.03) or overall survival (0.99, 0.87 to 1.12)."},"route":"/trials/keynote-921/","neighbours":{"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/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"prostate-failed-programmes","kind":"term","name":"Prostate cancer programmes that failed, and what each failure taught","route":"/terms/prostate-failed-programmes/"},{"id":"qol-pro","kind":"term","name":"Quality of life and patient-reported outcomes (QoL, PRO)","route":"/terms/qol-pro/"}],"trial":[{"id":"ca184-043-ipilimumab","kind":"trial","name":"CA184-043","route":"/trials/ca184-043-ipilimumab/"},{"id":"imbassador250","kind":"trial","name":"IMbassador250","route":"/trials/imbassador250/"},{"id":"keynote-641","kind":"trial","name":"KEYNOTE-641","route":"/trials/keynote-641/"},{"id":"keynote-991","kind":"trial","name":"KEYNOTE-991","route":"/trials/keynote-991/"}]}}