Cancer - Prostate(구연) (E-096) APALUTAMIDE FOR METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER in TITAN: POST-HOC ANALYSIS OF OUTCOMES IN PATIENTS WITH DE NOVO mCSPC VS PROGRESSION TO mCSPC AFTER LOCALIZED DISEASE AT DIAGNOSIS Urology, Gangnam Severance Hospital, Urology, Fudan University Shanghai Cancer Center, Medical Oncology, Huntsman Cancer Institute, University of Utah, Medical Oncology, Cerrahpaşa School of Medicine, Istanbul University-Cerrahpaşa, Urology, Kindai University Hospital Faculty of Medicine, Research & Development, Janssen, Research & Development, Janssen, Medical Oncology, BC Cancer and Vancouver Prostate Centre, Medical Oncology, Guy’s, King’s, and St Thomas’ Hospitals, and Sarah Cannon Research, Urology, Skåne University Hospital, Lund University Byung Ha Chung, Dingwei Ye, Neeraj Agarwal, Mustafa Özgüroğlu, Hirotsugu Uemura, Angela Lopez-Gitlitz, Gang Li, Kim Chi, Simon Chowdhury, Anders Bjartell Background: In TITAN, apalutamide (APA) added to ongoing androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS; HR, 0.48; 95% CI, 0.39-0.60; p < 0.001) and overall survival (OS; 0.67; 0.51-0.89; p = 0.005) in patients with metastatic castration-sensitive prostate cancer (mCSPC). / Objectives: We evaluated outcomes and safety profile of APA in TITAN patients with de novo (D1) mCSPC or progression to mCSPC after localized disease (D0) at initial diagnosis. / Materials and Methods: In this post hoc analysis of TITAN (N = 1052), patients were stratified by stage at initial presentation and assessed for baseline (BL) characteristics and outcomes: rPFS, OS, prostate-specific antigen (PSA) progression based on Prostate Cancer Working Group 2 criteria, and safety signals. HR and 95% CI were calculated using Cox proportional hazards model, p Values were calculated using unstratified log-rank test. / Results and Conclusion: At initial diagnosis, 144 patients had D0 (APA, n = 85; PBO, n = 59), 852 had D1 (APA, 411; PBO, 441) disease; metastasis status could not be determined in 56 patients. BL characteristics were comparable across subgroups, except fewer patients with Asian race had D0 (8 [6%]) than D1 (214 [25%]) disease. At 22.7 mo of median follow-up, APA significantly improved outcomes compared with PBO in both subgroups, reducing the risk of rPFS (D0: HR, 0.41 [95% CI, 0.22-0.77]; p = 0.004; D1: HR, 0.49 [95% CI, 0.36-0.62]; p < 0.0001), death (D0: HR, 0.40 [95% CI, 0.15-1.03]; p = 0.048; D1: HR, 0.72 [0.53-0.98]; p = 0.034), and PSA progression (D0: HR, 0.26 [0.13-0.50]; p < 0.0001; D1: HR, 0.26 [0.20-0.33]; p < 0.0001). Grade 3-4 treatment-emergent adverse events (TEAEs) were observed in 38% (32/84) vs 39% (23/59) of APA vs PBO patients with D0 disease and 43% (175/411) vs 42% (183/441) of APA vs PBO patients with D1 disease. Frequency of TEAEs of special interest in APA vs PBO patients was similar across D0 and D1 subgroups. In conclusion, treatment with APA in TITAN significantly improved rPFS, OS, and PSA progression compared with PBO in patients with D0 or D1 disease at diagnosis. The safety profile of APA by subgroup was consistent with the overall population. These results support the addition of APA to ADT for mCSPC patients regardless of disease stage at diagnosis.