11 Background: TITAN evaluated APA or PBO added to ADT in pts with mCSPC. Pts with high- and low-volume disease, prior docetaxel, prior treatment for localized disease, and prior ADT (≤ 6 mos) were eligible. At the first interim analysis, with 22.7 mos median follow-up, APA significantly improved dual primary end points of overall survival (OS) (hazard ratio [HR] 0.67) and radiographic progression-free survival (rPFS) (HR 0.48) compared with PBO (Chi et al. NEJM. 2019). At that time, OS analysis was first planned interim while rPFS was final. TITAN was unblinded, allowing pts without progression who were still receiving PBO to cross over to APA. Herein, we report the final analysis of efficacy and safety results from TITAN. Methods: 1052 mCSPC pts were randomized 1:1 to receive APA (240 mg QD) or PBO plus ADT. Time-to-event end points were analyzed by Kaplan-Meier method and Cox proportional hazards model. A preplanned sensitivity analysis for OS, accounting for crossover using inverse probability censoring weighted (IPCW) log-rank test, was conducted. No formal statistical retesting was performed; nominal p values were reported without multiplicity adjustment. Change from baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score was assessed using a mixed-effect repeated-measures model. Results: With 44 mos median follow-up, 405 OS events had occurred. After unblinding, 208 PBO pts (39.5%) crossed over to APA. Median treatment duration was 39.3 mos for the APA group, 20.2 mos for the entire PBO group, and 15.4 mos for the PBO→APA crossover group. OS was superior in the APA group compared with the PBO group despite crossover (Table). 48-mo survival rates were 65% (APA) vs 52% (PBO). Other end points also favored APA vs PBO (Table). Health-related quality of life (HRQoL), per total FACT-P, was maintained in the APA group through the study and was not different from the PBO group. Safety was consistent with previous reports. Conclusions: With close to 4 yrs of follow-up, the final analysis of TITAN demonstrated that in a broad population of pts with mCSPC, APA plus ADT provides an improvement in OS with a 35% reduction in risk of death, which increased to 48% reduction after adjusting for pts who crossed over from PBO to APA. In addition, there was consistent benefit with APA in other end points, including delaying castration resistance, and HRQoL continued to be maintained with an acceptable safety profile. Clinical trial information: NCT02489318. [Table: see text]