Abiraterone Acetate in Patients with Advanced Prostate Cancer

Chicago—An interim analysis of a randomized, phase 3 trial of patients with metastatic castration-resistant prostate cancer (mCRPC) who had not received chemotherapy found that those taking abiraterone acetate plus prednisone had a statistically significant improvement in progression-free survival compared with a group that received placebo plus prednisone.

The primary end point of progression-free survival was not reached after 16 months in the abiraterone acetate group because too few events had occurred (HR, 0.75; 95% CI, 0.61-0.93; P=.0097). Median progression-free survival in the placebo group was 8.3 months. The statistically significant benefit favoring abiraterone acetate was found in all subgroups.

The coprimary end point, median overall survival, was not met after 16 months in the abiraterone acetate group (HR, 0.75; 95% CI, 0.61-0.93; P=.0097) because too few events had occurred. Median overall survival was 27.2 months in the placebo group. The statistically significant benefit favoring abiraterone acetate was found in all subgroups.

Charles J. Ryan, MD, the study’s lead author and associate professor of clinical medicine at the University of California, San Francisco, presented the results during a late-breaking oral abstract session at the American Society of Clinical Oncology 2012 Annual Meeting in June.

Based on study results, Janssen Biotech, Inc, the manufacturer of the drug and the sponsor of the trial, intends to file for FDA approval in this patient population later this year.

In April 2011, the FDA approved abiraterone acetate (an oral medication) in combination with prednisone in patients with mCRPC who had received prior chemotherapy containing docetaxel. Abiraterone acetate is usually administered with prednisone to optimize the safety profile, according to Dr. Ryan.

The study’s protocol called for 3 interim analyses, including one analysis after 311 deaths had occurred, but the researchers performed this analysis after 332 deaths. The final analysis is planned after 773 deaths.

The researchers designed the trial to be double-blinded. However, after reviewing the interim results, the independent data monitoring committee met in February and unanimously recommended that the study be unblinded and patients in the placebo group be offered the opportunity to receive abiraterone acetate.

“As treating oncologists charged with providing safe and clinically beneficial therapies to our patients, these data merit consideration as providing a new standard approach in this highly prevalent patient population faced with an unmet medical need,” Dr. Ryan said.

More than 250,000 men die of prostate cancer worldwide each year, including approximately 30,000 people in the United States. Still, Dr. Ryan said that during the past decade there has been “significant progress” in prostate cancer therapies to improve survival, although, typically, this improvement has only been found in patients who underwent chemotherapy. Some trials have found a survival benefit in chemotherapy-naïve patients, but they did not indicate other clinical benefits such as objective response.

The study enrolled 1008 patients at 151 sites in 12 countries who were asymptomatic or mildly symptomatic, and defined as not requiring opioid analgesics or experiencing cancer-related pain for 1 month before study enrollment. They were randomized in a 1:1 ratio to receive 1000 mg of abiraterone acetate plus 5 mg of prednisone twice daily or placebo plus 5 mg of prednisone twice daily.

Dr. Ryan said the authors measured progression-free survival by central radiographic review and defined progression-free survival by using the published consensus criteria, including the development of ≥2 new bone lesions from baseline. Progression-free survival events also included death from any cause as well as disease progression as measured by RECIST (Response Evaluation Criteria in Solid Tumors).

The abiraterone acetate group also had statistically significant improvements in all of the secondary end points, including time to opiate use, time to chemotherapy initiation, time to Eastern Cooperative Oncology Group performance status deterioration, and time to prostate-specific antigen progression.