As we all anxiously wait for the FDA to finally make a determination about the pending application for approval of the investigational androgen biosynthesis inhibitor abiraterone acetate more data rolls in showing that supports the need to have a speedy approval. A new study published March 1, 2011, out of Italy adds support to the data that we need this drug. This randomized international trial showed an improved survival by almost 4 months in men with advanced prostate cancer that has become castration resistant and has progressed on docetaxel (Taxotere).

The men who were randomized to receive abiraterone had a median overall survival of 14.8 months compared with 10.9 months for the men in the placebo group (p<.0001). All secondary endpoints were significantly improved by treatment 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. Dr. de Bono added that some men have had prolonged responses to abiraterone. Dr. de Bono stated that two of his own patients have remained on continuous therapy for more than 4 years.

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 trial was halted in August 2010 when a planned interim analysis revealed a significant survival advantage in favor of abiraterone. The independent data monitoring committee recommended that men in the placebo arm should be offered treatment with abiraterone.

The study 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).

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%).

Now, we continue to wait for the FDA.

Joel T Nowak, M.A., M.S.W.