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 Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
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.