763PD - Updated overall survival (OS) from the phase 3 trial, CA184-043: Ipilimumab (Ipi) vs placebo (Pbo) in patients with post-docetaxel metastatic castr...

Date 28 September 2014
Event ESMO 2014
Session Genitourinary tumours, prostate
Topics Anticancer agents
Prostate Cancer
Therapy
Biological therapy
Presenter Karim Fizazi
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors K. Fizazi1, C. Drake2, E. Kwon3, A. Bossi4, A.J.M. van den Eertwegh5, H.I. Scher6, T. Beer7, M.B. McHenry8, D. Liu8, W.R. Gerritsen9, C. Logothetis10
  • 1Department Of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, 94800 - Villejuif CEDEX/FR
  • 2Department Of Urology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore/US
  • 3Urology And Immunology, Mayo Clinic, Rochester/US
  • 4Department Of Radiation Oncology, Institut Gustave Roussy, Villejuif/FR
  • 5Department Of Medical Oncology, VU University Medical Center, Amsterdam/NL
  • 6Medicine, Memorial Sloan-Kettering Cancer Center, 10128 - New York/US
  • 7Hematology & Medical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland/US
  • 8Global Biometrics Sciences, Bristol-Myers Squibb, 06492 - Wallingford/US
  • 9Department Of Medical Oncology, Radboud University Nijmegen Medical Centre, NL-1081 HV - Nijmegen/NL
  • 10Department Of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston/US

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,J&J,Medivation,Millennium,Pfizer, Sanofi Aventis,Ventana; 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.