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

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.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 Oct 31 [Epub]

Tomasz M Beer, Eugene D Kwon, Charles G Drake, Karim Fizazi, Christopher Logothetis, Gwenaelle Gravis, Vinod Ganju, Jonathan Polikoff, Fred Saad, Piotr Humanski, Josep M Piulats, Pablo Gonzalez Mella, Siobhan S Ng, Dirk Jaeger, Francis X Parnis, Fabio A Franke, Javier Puente, Roman Carvajal, Lisa Sengeløv, M Brent McHenry, Arvind Varma, Alfonsus J van den Eertwegh, Winald Gerritsen

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, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.

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