Ipilimumab Fails to Significantly Prolong Survival in Patients With Advanced Prostate Cancer
Bristol-Myers Squibb Company, the manufacturer of ipilimumab (Yervoy), released results from its phase III randomized double-blind study investigating the drug in men with metastatic castration-resistant prostate cancer. The study findings show that ipilimumab, a monoclonal antibody that blocks the action of CTLA-4, failed to meet its primary endpoint of prolonging overall survival.
However, antitumor activity was observed in other endpoints, including progression-free survival. Also, a subgroup analysis suggests that patients with less advanced disease may experience the most benefit from ipilimumab. The full results of the study will be presented at the 2013 European Cancer Congress on September 28, 2013.
The phase III trial (CA184-043) included nearly 800 patients with metastatic castration-resistant prostate cancer who had received prior docetaxel. Patients were randomly assigned 1:1 to receive bone-directed therapy at 8 Gy followed by ipilimumab at 10 mg/kg (n = 399) or placebo (n = 400). Treatment was administered every 3 weeks for four cycles and eligible patients received maintenance therapy every 3 months.
Study Results
The study found that patients in the ipilimumab arm had a median overall survival of 11.2 months compared with 10 months for patients in the placebo arm (hazard ratio [HR] = 0.85, 95% confidence interval [CI] = 0.72–1.00; P = .053), which did not meet the predetermined criteria for statistical significance. The 1- and 2-year survival rates for ipilimumab vs placebo were 47% vs 40%, and 26% vs 15%, respectively.
The secondary endpoint of progression-free survival favored ipilimumab treatment over placebo (HR = 0.70, 95% CI = 0.61–0.82). Additionally, a reduction in prostate-specific antigen of greater than or equal to 50% was experienced by 13.1% of patients receiving ipilimumab compared with 5.3% of patients receiving placebo. A prespecified subset analysis suggests that patients with lower disease burden experience the most benefit from ipilimumab.
“While we are disappointed that the primary endpoint of overall survival was not met, we remain encouraged that results in this advanced population support the potential role of immunotherapies for prostate cancer,” said Brian Daniels, MD, Senior Vice President, Global Development and Medical Affairs, Bristol-Myers Squibb, in a statement. “We are committed to continuing our development of Yervoy in prostate cancer.”
Further Trials Underway
A second phase III randomized double-blind trial comparing ipilimumab at 10 mg/kg vs placebo in patients with metastatic castration-resistant prostate cancer who have not received prior chemotherapy is expected to be completed by 2015. Ipilimumab is also being studied in phase III trials for adjuvant melanoma and non–small cell lung cancer. Ipilimumab was approved in 2011 for patients with unresectable or metastatic melanoma.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
