(UroToday.com) Published in 2020, the Phase 3 PROfound trial (NCT02987543) was a phase III randomized controlled trial of olaparib versus physician’s choice of enzalutamide or abiraterone in men with metastatic castration resistant prostate cancer (mCRPC) with alterations in at least one of 15 homologous recombination repair genes who had disease progression on next-generation hormonal agent.1,2 The trial met its primary endpoint of an improvement in radiographic progression-free survival with olaparib in mCRPC with alterations in BRCA1, BRCA2, or ATM (Cohort A).1 Key secondary endpoints, including improved overall survival in Cohort A, were also met.2 These results led to the approval of olaparib treatment in patients with mCRPC who had progressed on prior enzalutamide or abiraterone with homologous recombination repair alterations in the USA and with alterations in BRCA1 and/or BRCA2 in the European Union. At the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Johann De Bono and colleagues presented results of gene-by-gene analysis of olaparib antitumor activity among the 15 prespecified homologous recombination repair genes.