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. Patien...

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Published in:	Journal of clinical oncology Vol. 35; no. 1; pp. 40 - 47
Main Authors:	Beer, Tomasz M, Kwon, Eugene D, Drake, Charles G, Fizazi, Karim, Logothetis, Christopher, Gravis, Gwenaelle, Ganju, Vinod, Polikoff, Jonathan, Saad, Fred, Humanski, Piotr, Piulats, Josep M, Gonzalez Mella, Pablo, Ng, Siobhan S, Jaeger, Dirk, Parnis, Francis X, Franke, Fabio A, Puente, Javier, Carvajal, Roman, Sengeløv, Lisa, McHenry, M Brent, Varma, Arvind, van den Eertwegh, Alfonsus J, Gerritsen, Winald
Format:	Journal Article
Language:	English
Published:	United States 01-01-2017
Subjects:	Adult Aged Aged, 80 and over Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - therapeutic use Antineoplastic Agents - adverse effects Antineoplastic Agents - therapeutic use Asymptomatic Diseases Bone Neoplasms - blood Bone Neoplasms - drug therapy Bone Neoplasms - secondary Diarrhea - chemically induced Disease-Free Survival Double-Blind Method Humans Ipilimumab Male Middle Aged Prostate-Specific Antigen - blood Prostatic Neoplasms, Castration-Resistant - blood Prostatic Neoplasms, Castration-Resistant - drug therapy Prostatic Neoplasms, Castration-Resistant - pathology Survival Rate
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-News-3 content type line 23
ISSN:	0732-183X 1527-7755
DOI:	10.1200/JCO.2016.69.1584