Background: Addition of androgen receptor signaling inhibitors to ADT + DOC has been shown to improve clinical outcomes in pts with mCSPC. TITAN, a placebo-controlled phase 3 study, showed that APA + ADT improved overall survival (OS) and other clinical outcomes in mCSPC (Chi, J Clin Oncol 2021). This post hoc analysis of TITAN evaluated outcomes in pts who had received DOC prior to treatment with APA + ADT versus those who did not. Methods: In TITAN, 1052 pts were randomized 1:1 to APA (240 mg QD) or placebo added to ongoing ADT. We assessed radiographic progression-free survival (rPFS), OS, and time to prostate-specific antigen (PSA) progression in pts receiving DOC and ADT prior to adding APA vs those receiving only ADT plus APA. Outcomes by prior DOC were also assessed in pts with high- or low-volume disease at randomization (baseline [BL]) per adapted CHAARTED criteria, or those with matched BL characteristics. A Cox proportional hazards model was used to derive hazard ratios (HRs) and p values. rPFS was assessed using the first interim analysis cutoff (23 mo median follow-up); OS and time to PSA progression were assessed using the final analysis cutoff (44 mo median follow-up). Results: A total of 58/525 (11%) pts from the APA + ADT group had received DOC prior to randomization: 76% (n = 44) had high-volume disease, 62% (n = 36) had bone-only metastases, 16% (n = 9) had visceral metastases, and 59% (n = 34) had > 10 bone lesions. In the overall APA-treated population and in the subset of pts with high-volume disease, OS, rPFS, and time to PSA progression were similar in those who received prior DOC and those who did not (Table). Pts with low-volume disease also had similar results, although the number of pts was small. Clinical outcomes in pts with matched BL characteristics (including PSA and time from initial diagnosis to randomization, among others) were similar regardless of prior use of DOC (Table). The safety profile of APA was not substantially different between pts with or without prior DOC. Limitations of this analysis include lack of data on tumor volume and other disease characteristics at the initiation of prior DOC treatment; interpretation was based on small number of pts with prior DOC (only 11% of TITAN pts), most notably in the rPFS analysis. Conclusions: Prior use of DOC in pts with mCSPC did not further improve clinical benefits of APA + ADT in TITAN. Clinical trial information: NCT02489318.