Prosper: a Phase 3 Study of Enzalutamide in Non-Metastatic (M0) Castration-Resistant Prostate Cancer (Crpc) Patients

Abstract

Background: Prostate cancer growth is dependent on androgen receptor (AR) signaling. There is no standard of care for patients with M0 CRPC and most patients will eventually develop metastatic disease despite ongoing androgen deprivation therapy (ADT). In a recent study, patients with a PSA >8 ng/mL or PSA doubling time of <10 months had a median time to bone metastasis of only 2 years (Smith et al. Lancet 2012; 379: 39–46). Enzalutamide (formerly MDV3100) is an oral AR inhibitor that targets multiple steps in the AR signaling pathway. In two large Phase 3 studies, enzalutamide was shown to prolong overall survival and radiographic progression‐free survival in patients with metastatic CRPC. The objective of the PROSPER trial is to evaluate the efficacy and safety of enzalutamide in M0 CRPC patients. Trial design: PROSPER is a randomized, double‐blind, placebo‐controlled, Phase 3 study (NCT02003924) initiated in December 2013 and involving more than 200 sites in the United States, Canada, Europe, South America and the Asia Pacific region. Eligibility criteria include: asymptomatic M0 CRPC; PSA doubling time ≤10 months; screening PSA ≥2 ng/mL; and adequate hematologic, hepatic, and renal function. Approximately 1560 patients will have continued ADT and will be randomized 2:1 to enzalutamide 160 mg/day or placebo. Patients will be stratified by PSA doubling time (<6 vs 6‐10 months) and baseline use of bone‐targeting agent (yes vs no).The primary endpoint is metastasis‐free survival based on central independent review of whole‐body radionuclide bone scans for bone disease assessment and CT or MRI scans for soft tissue disease assessment. Imaging will be undertaken at screening and every 16 weeks post randomization until radiographic progression. The study has 90% power to detect a target hazard ratio of 0.75 based on a 2‐sided log‐rank test at an overall significance level of 0.05. Secondary endpoints include: overall survival; time to pain progression; time to opiate use for prostate cancer pain; time to first use of cytotoxic chemotherapy; time to first use of new antineoplastic therapy; time to PSA progression; PSA response; and quality of life as assessed by FACT‐P, EQ‐5D‐5L and QLQ‐PR25. This abstract was accepted and previously presented at the 2014 ASCO Annual Meeting (TPS5094). Disclosure: C.N. Sternberg: Astellas; Honoraria Johnson & Johnson; Honoraria Ipsen; Honoraria Bayer; Honoraria Millenium; Honoraria; K. Fizazi: Astellas/Medivation; Advisory boards, speaker; F. Saad: Medivation/Astellas; Grants, personal fees, non‐financial support Janssen; Grants, personal fees, non‐financial support; N.D. Shore: Serves as a consultant or advisory relationship with Astellas and Medivation, Inc.; A. Heidenreich: Receives honoraria from Astellas, Amgen, Bayer, Dendreon, Ferring, IPSEN, Janssen, Pfizer, Takeda and Sanofi. Receives research funding from Astellas and Sanofi. Acts as a consultant or advisory relationship with Astellas, Bayer, Janssen, Sanofi; M. Hirmand: Is employed by Medivation as VP Clinical Development and has stock; F.G. Perabo: Astellas; employee; Z. Khondker: Employed by Medivation, Inc as Senior Biostatistician, and has stock with Medivation, Inc.; K. Modelska: Employed by Medivation as Senior Director Clinical Development and has stock with Medivation, Inc.; M. Hussain: Receives research funding from Medivation and contact with University of Michigan.