{"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":[],"cancers":["prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"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":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"}],"drug":[{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"}],"trial":[{"id":"profound","kind":"trial","name":"PROfound","route":"/trials/profound/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}