763PD - Updated Overall Survival (Os) from the Phase 3 Trial, Ca184-043: Ipilimumab (Ipi) Vs Placebo (Pbo) in Patients with Post-Docetaxel Metastatic Castration-Resistant Prostate Cancer (Mcrpc)

Abstract

ABSTRACT Aim: Ipi is a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) to augment antitumor immune responses. The phase 3 trial, CA184-043, evaluated OS with radiotherapy (RT) followed by Ipi or Pbo in patients (pts) with advanced mCRPC. As reported previously, the primary endpoint was not met [HR (95% CI): 0.85 (0.72-1.00); P = 0.053] (Kwon ED, et al. Lancet Oncol. 2014; in press). Here, we report updated OS data with an additional year of follow-up from the primary analysis (2-yr minimum). Methods: 799 pts were randomized to receive a single dose of RT to bone metastases followed by either Ipi (N = 399) or Pbo (N = 400). Updated OS analysis was performed on the intention-to-treat (ITT) population. Prespecified and exploratory subset analyses based on Kaplan-Meier/Cox methodology were performed using known prognostic factors for OS in mCRPC. Results: Updated OS analysis (ITT population), with survival rates up to 3 yrs, was consistent with the primary analysis (Table). Also consistent with previous reports, prespecified subgroup analyses suggest greater activity in pts with lower disease burden [e.g., Ipi vs. Pbo, pts with (HR 1.17, 0.89–1.53) or without (0.74, 0.61–0.89) visceral metastases]. The safety profile with extended follow-up was similar to that reported previously, which included immune-related AEs (irAEs) (gastrointestinal, dermatologic, endocrine, and hepatic). Most irAEs were manageable with established Ipi treatment algorithms. Ipi + RT Pbo + RT Median OS (95% CI) 11.2 mo (9.6–12.6) 10.0 mo (8.4–11.2) HR (95% CI) 0.84 (0.72–0.98) Log-rank * P = 0.03 1-Year OS rate 47% 41% 2-Year OS rate 25% 17% 3-Year OS rate ** 12% 6% * Exploratory analysis (for descriptive purposes only). ** 27 pts (17 Ipi, 10 Pbo) included in the risk set at 36 mo. Conclusions: With an additional year of follow-up, the activity observed for Ipi + RT in post-docetaxel mCRPC pts is maintained. In addition, subgroup analyses suggest pts with lower disease burden may be more likely to benefit from Ipi treatment. Long-term OS and Ipi benefit in mCRPC pts with lower disease burden (i.e., no visceral metastases) will be evaluated in the ongoing phase 3 study, CA184-095. Disclosure: K. Fizazi: Advisory board: Bristol-Myers Squibb; C.G. Drake: Sponsored research: Aduro Biotech, Bristol-Myers Squibb, Janssen; consultant: Bristol-Myers Squibb, Compugen, Dendreon, Pfizer, Roche/Genentech, NexImmune; .D. Kwon: Advisory board: NCI GU Steering Committee. Dr. Kwon and Mayo Clinic have licensed technology related to immunotherapy to Bristol-Myers Squibb, MedImmune, Amplimune, and Medarex; A.J. van den Eertwegh: Advisory board: Bristol-Myers Squibb, Astellas, Janssen-Cilag B.V., Sanofi. Honoraria for presentations about ipilimumab/prostate cancer: Bristol-Myers Squibb, Sanofi, Janssen-Cilag; H.I. Scher: Ad board:Dendreon,Endo/Orion,Genentech,Novartis,OrthoBiotech,Aragon,BMS,Celgene,Exelixis,FoundationMedicine,Janssen,JJ Spons.research: Aragon,BMS,Exelixis,Janssen,Medivation; T.M. Beer: Corporate-sponsored research: Bristol-Myers Squibb; M.B. McHenry: Employee of Bristol-Myers Squibb and owns Bristol-Myers Squibb stock; D. Liu: Employee of Bristol-Myers Squibb; owns Bristol-Myers Squibb stock; W.R. Gerritsen: Advisory board: Aglaia Biomedical Ventures, Amgen, Bayer, Bristol-Myers Squibb, Ipsen, Janssen, Merck, and Sanofi; speaker's honoraria: Astellas, Bristol-Myers Squibb, and Janssen; C. Logothetis: Corporate-sponsored research: Johnson & Johnson; honoraria: Johnson & Johnson.All other authors have declared no conflicts of interest.