762PDIMPACT OF ENZALUTAMIDE ON SKELETAL RELATED EVENTS (SRES), PAIN AND QUALITY OF LIFE (QOL) IN THE PREVAIL TRIAL.

ABSTRACT Aim: Enzalutamide (ENZ) improved overall survival vs. placebo (PL) in PREVAIL, a phase 3 trial in asymptomatic/mildly symptomatic chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) [Beer et al, ASCO GU 2014]. PREVAIL also prospectively evaluated SREs, pain and QoL. Methods: Pts were randomized to ENZ (160mg/day; n = 872) or PL (n = 845). SREs were assessed throughout the study and time to 1st SRE measured. QoL was assessed at baseline (BL) and during treatment (tx) on the FACT-P and EQ-5D; changes from BL over time were compared using repeated measures analyses. Pain was assessed with the BPI-SF at BL, and months (mo) 3 and 6. Pts with BL and ≥1 post-BL score were analyzed using pre-specified criteria for clinically meaningful pain progression (pain severity: increase ≥30% from BL; pain interference: increase ≥50% of BL standard deviation) and QoL deterioration (Cella et al, VIH 2009; Pickard et al, HQOL 2007). Results: Median tx duration was 16.6 (ENZ) and 4.6 (PL) mo; BL pain and QoL scores were similar between arms. Overall, 32% (ENZ) and 37% (PL) of pts reported at least one SRE. Compared to PL, ENZ significantly reduces the risk of 1st SRE occurrence (hazard ratio: 0.72 [0.61, 0.84], p Time to 1st deterioration (mo), median (95% Cl) ENZ (n = 872) PL (n = 845) P-value Hazard ratioa (95% CI) EQ-5D instrument Visual analogue scale 22.14 (19.35;27.66) 13.83 (11.07;16.59) 0.67 (0.56;0.80) FACT-P instrument Physical well-being 10.84 (8.31;11.07) 5.55 (5.49;5.62) 0.74 (0.65;0.85) Functional well-being 8.54 (8.31;11.07) 3.09 (2.86;5.55) 0.72 (0.62;0.82) Emotional well-being 19.48 (16.59;25.07) 11.01 (8.25;11.40) 0.67 (0.57;0.79) Social well-being 24.87 (14.16;NYR) 8.51 (6.01;13.86) 0.74 (0.63;0.86) Prostate Cancer Subscale 5.65 (5.55;8.31) 2.83 (2.79;2.96) 0.69 (0.60;0.78) FACT-P total score 11.30 (11.07;13.86) 5.55 (5.49;5.59) 0.62 (0.54;0.72) Pain progression, n(%) Pain severity 329/802 (41) 317/628 (50) Pain interference 247/788 (31) 255/613 (42) Conclusions: In PREVAIL, in addition to overall survival benefit, ENZ was also associated with clinically significant patient benefits compared to PL, including a delay in time to 1st SRE, superior QoL, a delay in QoL deterioration, and significantly lower proportion of pts with pain. Disclosure: Y. Loriot: Consultant/Advisory: Astellas Research Funding: Astellas Other: Sanofi, Janssen, Bayer, Cellgene; K. Miller: Consulting: Astellas/Medivation Consultancy: Astellas, Amgen, Janssen, Medivation, Novartis, Roche Lectures: Novartis, Janssen, Pierre-Fabre; C.N. Sternberg: Honoraria: Astellas, Johnson & Johnson, Ipsen, Bayer, Millenium; K. Fizazi: Advisory Board: Astellas/Medivation Speaker: Astellas/Medivation; J.S. de Bono: Astellas/Medivation; S. Chowdhury: Advisory Board/Lecture: Astellas, Janssen, Sanofi-Aventis, Dendreon Speaker: GSK; C. Higano: Research funding: Astellas/Medivation, Algeta, Aragon, Dendreon, Sanofi Consultant/Advisory: Astellas/Medivation, Dendreon, Bayer, Johnson & Johnson; S. Noonberg: Employee: Medivation; S. Holmstrom, F.G. Perabo and D. Phung: Employee: Astellas; H. Mansbach: Employee: Medivation; C. Ivanescu: Astellas: payment for writing or reviewing a manuscript, provision of writing assistance or administrative support, consultancy; K. Skaltsa: Astellas: Payment for writing or reviewing a manuscript, provision of writing assistance or administrative support, consultancy; T. Beer: Research Funding: Astellas/Medivation, Janssen Consultant: Janssen; B. Tombal: Advisor: Astellas/Medivation, Ferring Speaker: Astellas, Ferring