767P - Response Rates and Outcomes with Enzalutamide for Patients with Metastatic Castration Resistant Prostate Cancer and Visceral Disease in the Prevail Trial

Abstract

ABSTRACT Aim: In the PREVAIL trial, enzalutamide, an androgen receptor signaling inhibitor, significantly improved overall survival (OS) (HR, 071; p Methods: PREVAIL was a Phase 3 multinational, double-blind study in chemotherapy-naive men with asymptomatic or mildly symptomatic mCRPC. Co-primary endpoints were OS and rPFS. Best soft tissue objective response, a secondary endpoint, was defined as partial or complete response (PR or CR) per RECIST 1.1 criteria in patients with measurable disease at baseline. Results: A total of 1717 men were randomized (1715 treated) including 1513 (88.1%) without and 204 (11.9%) with visceral disease at screening (139 lung, 74 liver and 9 both). Patients with visceral disease had higher baseline median PSA than those without visceral disease (72.5 ng/mL and 46.8 ng/mL, respectively), worse performance status (38.2% and 31.1% ECOG PS = 1), and higher rates of lymph node disease (57.8% and 49.8%), but similar rates of bone disease (80.4% and 83.7%). Adverse event rates were similar to the full study population. Conclusions: Visceral metastases were permitted in the PREVAIL trial of men with chemotherapy-naive mCRPC. Enzalutamide was active in this small group of patients; post-hoc analyses showed benefit vs placebo on OS, rPFS, and secondary endpoints. Response rates were higher for lung vs liver metastases. These results support androgen receptor signaling as an important target in prostate cancer with visceral metastases. Response Rates and Study Outcomes in PREVAIL Total Visceral Disease Cohort Lung and/or Liver (n = 204) Median (months) Enzalutamide/Placebo HR (95% CI) rPFS NYR/3.6 0.28 (0.16, 0.49) OS 27.8/22.8 0.82 (0.55, 1.23) Time to cytotoxic chemotherapy 22.6/6.6 0.30 (0.20, 0.45) Time to PSA progression (PCWG2 criteria) 11.1/2.9 0.16 (0.10, 0.26) Time to first skeletal-related event 29.5/NYR 0.69 (0.43, 1.11) Visceral Disease Cohort With Baseline Measurable Soft Tissue Disease * Liver Lung Enzalutamide (N= 31) Placebo (N= 28) Enzalutamide (N= 25) Placebo (N= 36) Best Objective Response (95% CI) 29.0% (14.2-48.0) 0.0 (0.0 - 12.3) 60.0% (38.7-78.9) 0.0% (0.0- 9.7) Complete Response 6.5% 0.0% 8.0% 0.0% Partial Response 22.6% 0.0% 52.0% 0.0% * Defined as at least one target lesion per RECIST 1.1. Disclosure: C. Higano: Consultant: Astellas/Medivation, Bayer, Dendreon, Johnson & Johnson Research Funding: Alegra, Aragon, Astellas/Medivation, Dendreon, Sanofi; S. Chowdhury: Advisory Board/Lectures: Astellas, Janssen Cilag, Sanofi-Aventis, Dendreon Speaker: GSK; Y. Loriot: Consultant/Advisory: Astellas Research Funding: Astellas Other: Sanofi, Cellgene, Bayer, Jansen; C.N. Sternberg: Honoraria: Astellas, Johnson & Johnson, Ipsen, Bayer, Millenium; J.S. de Bono: Astellas/Medivation; B. Tombal: Advisor: Medivation, Astellas, Ferring Speaker: Astellas, Ferring; F.G. Perabo: Employee: Astellas Pharma; D. Forer, S. Noonberg and H. Mansbach: Employee: Medivation; T. Beer: Research Funding: Astellas/Medivation, Janssen Consultant: Janssen. All other authors have declared no conflicts of interest.