Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer
Top Cited Papers
- 1 January 2017
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 35 (1), 40-47
- https://doi.org/10.1200/jco.2016.69.1584
Abstract
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. 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). 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. 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.Keywords
This publication has 29 references indexed in Scilit:
- Alpha Emitter Radium-223 and Survival in Metastatic Prostate CancerNew England Journal of Medicine, 2013
- Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 studyThe Lancet Oncology, 2012
- Increased Survival with Enzalutamide in Prostate Cancer after ChemotherapyNew England Journal of Medicine, 2012
- CTLA-4 Blockade with Ipilimumab: Long-term Follow-up of 177 Patients with Metastatic MelanomaClinical Cancer Research, 2012
- Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trialThe Lancet, 2010
- Improved Survival with Ipilimumab in Patients with Metastatic MelanomaNew England Journal of Medicine, 2010
- Prostate cancer as a model for tumour immunotherapyNature Reviews Immunology, 2010
- Sipuleucel-T Immunotherapy for Castration-Resistant Prostate CancerNew England Journal of Medicine, 2010
- Design and End Points of Clinical Trials for Patients With Progressive Prostate Cancer and Castrate Levels of Testosterone: Recommendations of the Prostate Cancer Clinical Trials Working GroupJournal of Clinical Oncology, 2008
- Peripheral T cell tolerance occurs early during spontaneous prostate cancer development and can be rescued by dendritic cell immunizationEuropean Journal of Immunology, 2004