{"entity":{"id":"propel","kind":"trial","name":"PROpel","aka":[],"tldr":"Showed PARP inhibitor plus abiraterone delays progression in first-line mCRPC, with the largest benefit in BRCA-mutant men.","summary":"PROpel, trial NCT03732820 sponsored by AstraZeneca and Merck and reported in 2022, showed that adding the PARP inhibitor olaparib to abiraterone delays progression in first-line metastatic castration-resistant prostate cancer regardless of mutation status, with the largest benefit in men with BRCA mutations. It randomised 796 unselected men and met its primary radiographic progression-free survival endpoint, but overall survival was not significantly improved in the whole population, so the FDA restricted approval in 2023 to BRCA-mutant disease while the EMA approved the combination for all comers. OnCo links it to BRCA1 and BRCA2 as targets, to olaparib and abiraterone acetate, and its findings are consistent with MAGNITUDE and TALAPRO-2 in HRR-mutant disease. Whether unselected men gain enough to justify the toxicity is the open question, and labels differ by region.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT03732820","url":"https://clinicaltrials.gov/study/NCT03732820"},{"label":"NICE TA951: olaparib with abiraterone for untreated hormone-relapsed metastatic prostate cancer","url":"https://www.nice.org.uk/guidance/ta951"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["parp-inhibitor"],"targets":["brca"],"drugs":["olaparib","abiraterone"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["prostate-hrr-eligibility","prostate-uk-drug-approvals"],"trials":["talapro-2","magnitude","profound"],"people":[],"bottlenecks":[],"keyPapers":["paper-propel-lancet-oncol-2023"],"journals":[],"dependsOn":[],"notes":["In England NICE TA951 recommends olaparib with abiraterone and prednisone or prednisolone within its marketing authorisation for untreated hormone-relapsed metastatic prostate cancer in adults who cannot have or do not want chemotherapy, subject to the commercial arrangements. The committee noted that usual treatment is abiraterone or enzalutamide, that the trial shows the combination increases how long people live and how long before the cancer worsens compared with abiraterone alone, and that no direct comparison with enzalutamide exists."],"nct":"NCT03732820","phase":"3","setting":"First-line mCRPC, all-comers: abiraterone + olaparib vs abiraterone + placebo","sponsor":"AstraZeneca / Merck","result":"rPFS HR 0.66 (ITT); OS HR 0.81 (NS).","started":"2018-10-31","startedType":"actual","yearReported":2022,"enrolled":796,"enrolledBasis":"randomised","enrolledNote":"ClinicalTrials.gov lists 895 participants (actual); 1,103 patients were screened and 796 randomised (399 olaparib, 397 placebo) in the primary analysis.","outcomes":[{"endpoint":"Radiographic progression-free survival (investigator), all comers","primary":true,"unit":"months","arms":[{"name":"Olaparib + abiraterone","n":399,"value":24.8},{"name":"Placebo + abiraterone","n":397,"value":16.6}],"hr":0.66,"ci":[0.54,0.81],"p":"<0.001","source":"https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200043"},{"endpoint":"Overall survival, all comers","unit":"months","arms":[{"name":"Olaparib + abiraterone","value":42.1,"note":"Not significant; larger effect in BRCA-mutant"},{"name":"Placebo + abiraterone","value":34.7}],"hr":0.81,"ci":[0.67,1],"source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00382-9/fulltext"}],"replication":"Consistent with MAGNITUDE and TALAPRO-2 in HRR-mutant disease; the all-comers benefit is debated and labels differ by region."},"route":"/trials/propel/","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":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"}],"drug":[{"id":"abiraterone","kind":"drug","name":"Abiraterone acetate","route":"/drugs/abiraterone/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"term":[{"id":"prostate-uk-drug-approvals","kind":"term","name":"Prostate cancer drugs in England: what NICE recommends, and what it refuses","route":"/terms/prostate-uk-drug-approvals/"},{"id":"prostate-hrr-eligibility","kind":"term","name":"Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters","route":"/terms/prostate-hrr-eligibility/"}],"trial":[{"id":"magnitude","kind":"trial","name":"MAGNITUDE","route":"/trials/magnitude/"},{"id":"profound","kind":"trial","name":"PROfound","route":"/trials/profound/"},{"id":"talapro-2","kind":"trial","name":"TALAPRO-2","route":"/trials/talapro-2/"},{"id":"triton3","kind":"trial","name":"TRITON3","route":"/trials/triton3/"}],"paper":[{"id":"paper-propel-lancet-oncol-2023","kind":"paper","name":"Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial","route":"/key-papers/paper-propel-lancet-oncol-2023/"}],"idea":[{"id":"idea-cost-low-dose-abiraterone-food","kind":"idea","name":"Prescribe a quarter dose of abiraterone with breakfast","route":"/ideas/idea-cost-low-dose-abiraterone-food/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}