Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

Author:

Beer Tomasz M.1,Kwon Eugene D.1,Drake Charles G.1,Fizazi Karim1,Logothetis Christopher1,Gravis Gwenaelle1,Ganju Vinod1,Polikoff Jonathan1,Saad Fred1,Humanski Piotr1,Piulats Josep M.1,Gonzalez Mella Pablo1,Ng Siobhan S.1,Jaeger Dirk1,Parnis Francis X.1,Franke Fabio A.1,Puente Javier1,Carvajal Roman1,Sengeløv Lisa1,McHenry M. Brent1,Varma Arvind1,van den Eertwegh Alfonsus J.1,Gerritsen Winald1

Affiliation:

1. Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis,...

Abstract

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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