Background: Optimal sequencing of therapies for mCRPC is not established. In the Phase III PROfound study (NCT02987543), ola significantly prolonged radiographic progression-free survival (rPFS) vs physician’s choice of new hormonal agent (pcNHA) in pts with mCRPC and an alteration in genes with a direct or indirect role in HRR. We report exploratory subgroup analyses by prior taxane (yes vs no). Methods: Men with mCRPC that had progressed on prior NHA were randomized to ola (tablets; 300 mg bid) or pcNHA (enzalutamide or abiraterone). Pts had alterations in BRCA1, BRCA2 or ATM (Cohort A) or ≥1 of 12 other prespecified genes with a direct or indirect role in HRR (Cohort B). Stratification factors were prior taxane use and measurable disease. rPFS was assessed by blinded independent central review with RECIST v1.1 + PCWG3. Results: Subgroup analyses of rPFS and overall survival (OS) favored ola vs pcNHA irrespective of prior taxane in Cohort A, Cohorts A+B and pts with a BRCA1 and/or BRCA2 or CDK12 alteration (Table). In the ATM subgroup hazard ratio (HR) point estimates for rPFS and OS were lower in pts who had received prior taxane vs pts who had not, but 95% CIs overlapped and pt numbers were small so data should be interpreted with caution. Conclusions: The benefit of ola over pcNHA in pts with mCRPC and HRR gene alterations was generally independent of prior taxane status in the overall study population.Clinical trial information: NCT02987543

m, months; N, no; NR, not reached; Y, yes