{"entity":{"id":"paper-profound-nejm-2020","kind":"paper","name":"PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations","aka":[],"tldr":"In men with metastatic castration-resistant prostate cancer carrying BRCA1, BRCA2 or ATM alterations who had progressed on hormonal therapy, the PARP inhibitor olaparib delayed progression and lengthened survival compared with another hormonal agent.","summary":"Phase 3 trial of 387 men with metastatic castration-resistant prostate cancer progressing on enzalutamide or abiraterone, with alterations in BRCA1, BRCA2 or ATM (cohort A) or 12 other homologous recombination genes (cohort B), randomised 2:1 to olaparib or physician's choice of enzalutamide or abiraterone.\n\nIn cohort A median progression-free survival was 7.4 versus 3.6 months (hazard ratio 0.34) and median overall survival 19.1 versus 14.7 months (hazard ratio 0.69 despite crossover); benefit was driven mainly by BRCA2.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa1911440"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32343890/"}],"tags":[],"related":["prostate-roadmap","paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","paper-fizazi-triton3-rucaparib-nejm-2023","idea-prostate-hrr-testing-at-metastatic-diagnosis"],"cancers":["prostate-mcrpc","prostate"],"sections":[],"technologies":[],"targets":["brca","atm","cdk12","parp"],"drugs":["olaparib"],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","base-excision-repair-parp","synthetic-lethality-map"],"terms":["germline-vs-somatic","gbrca-mutation","hrd"],"trials":["profound"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1911440","pmid":"32343890","authors":"de Bono J, Mateo J, Fizazi K, et al.","paperType":"rct","findings":["Cohort A: median progression-free survival 7.4 vs 3.6 months; hazard ratio 0.34.","Cohort A: median overall survival 19.1 vs 14.7 months; hazard ratio 0.69."],"whatItMeans":"Germline and tumour testing for homologous recombination repair genes is now standard in metastatic prostate cancer, and olaparib is approved for BRCA-mutated disease after a hormonal agent.","caveats":["Benefit in ATM and the cohort B genes was weak or absent.","The comparator, a second hormonal agent, has limited activity after progression on the first."],"changedPractice":true,"participants":387},"route":"/key-papers/paper-profound-nejm-2020/","neighbours":{"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/"}],"paper":[{"id":"paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","kind":"paper","name":"TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer","route":"/key-papers/paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015/"},{"id":"paper-abida-triton2-rucaparib-brca-jco-2020","kind":"paper","name":"TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration","route":"/key-papers/paper-abida-triton2-rucaparib-brca-jco-2020/"},{"id":"paper-fizazi-triton3-rucaparib-nejm-2023","kind":"paper","name":"TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer","route":"/key-papers/paper-fizazi-triton3-rucaparib-nejm-2023/"}],"idea":[{"id":"idea-prostate-hrr-testing-at-metastatic-diagnosis","kind":"idea","name":"Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later","route":"/ideas/idea-prostate-hrr-testing-at-metastatic-diagnosis/"}],"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/"}],"target":[{"id":"atm","kind":"target","name":"ATM","route":"/targets/atm/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"cdk12","kind":"target","name":"CDK12","route":"/targets/cdk12/"},{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"}],"drug":[{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"}],"pathway":[{"id":"base-excision-repair-parp","kind":"pathway","name":"Base excision repair, PARP & alkylation damage","route":"/pathways/base-excision-repair-parp/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"id":"synthetic-lethality-map","kind":"pathway","name":"Synthetic lethality: paired dependencies","route":"/pathways/synthetic-lethality-map/"}],"term":[{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"}],"trial":[{"id":"profound","kind":"trial","name":"PROfound","route":"/trials/profound/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}