Treatment with the androgen biosynthesis inhibitor abiraterone acetate improved survival by almost 4 months in men with castration-resistant prostate cancer that had progressed on docetaxel (Taxotere).
Patients randomized to abiraterone had a median overall survival of 14.8 months compared with 10.9 months in the placebo group (p<.0001). All secondary endpoints were significantly improved by treatment with the novel androgen inhibitor, as reported at the 2010 European Society for Medical Oncology annual congress in Milan, Italy.
"While 3.9 months may not seem like much, in the history of prostate cancer, only four drugs have ever shown a survival benefit," said first author Johann S. de Bono, MD, PhD, an oncologist with the Royal Marsden NHS Foundation Trust in Sutton, United Kingdom.
Abiraterone targets the CYP17 enzyme necessary for androgen biosynthesis. The drug inhibits both adrenal and intratumoral androgen production.
Dr. de Bono presented results from a trial involving 1,195 patients who were randomized 2:1 to abiraterone plus prednisone or placebo plus prednisone. Overall survival was the primary endpoint, and the trial was powered to detect a 20% improvement in survival.
The patient population had a median age of 69 years, and about 90% had an Eastern Cooperative Oncology Group performance status of 0-1. Additionally, 44% of the patients had significant pain, 28% had exposure to two prior chemotherapy regimens, and 70% had radiographic evidence of disease progression. About 90% of the patients had bone involvement, and 25% to 30% had visceral metastases.
The magnitude of improvement in overall survival was similar in patients who had received one prior chemotherapy regimen (15.4 vs. 11.5 months) or two prior regimens (14.0 vs. 10.3 months). Additional subgroup analyses showed a consistent survival advantage with abiraterone.
The abiraterone group also had a significantly longer median duration of time to PSA progression (10.2 vs 6.6 months, p<.0001) and radiologically confirmed progression-free survival (5.6 vs. 3.6 months, p<.0001), as well as a higher PSA response rate (38% vs. 10%, p<.0001).
Adverse events similar between arms
The incidence of adverse events, serious adverse events, and adverse events leading to discontinuation was similar between the two treatment arms. The most common adverse events in the abiraterone arm were fluid retention (30.5%), hypokalemia (17.1%), abnormal liver function tests (10.4%), hypertension (9.7%), and cardiac disorders (13.3%).
The trial results add to what has proved to be a period of unprecedented progression in the treatment of castration-resistant prostate cancer, Dr. de Bono said. In addition to abiraterone, two other therapies achieved statistically significant survival advantages in randomized clinical trials: sipuleucel-T immunotherapy (Provenge) and cabazitaxel (Jevtana). Previously, only docetaxel had evidence of improved overall survival.
"If abiraterone is approved, I can see it and the other new drugs being used sequentially to try and make advanced prostate cancer more of a chronic disease," said Dr. de Bono.
Invited discussant Cora Sternberg, MD, chief of medical oncology at Camillo and Forliani Hospitals in Rome, said, "These are the most impressive results I have seen in a long time in this population.
"I do believe we have a breakthrough for advanced prostate cancer."
Dr. de Bono has received honoraria and consulting fees from Merck, Pfizer, AstraZeneca, Johnson & Johnson, Medivation, and Genentech. Dr. Sternberg has served as a consultant/adviser for GlaxoSmithKline.