New agents combined with standard therapies are now providing statistically significant improvements in disease progression and longer overall survival (OS) in men with metastatic castration-resistant prostate cancer. Studies pertaining to combination therapies involving newer agents, such as abiraterone acetate, enzalutamide, and degarelix, were presented at the 2013 ASCO Genitourinary Cancers Symposium, held on February 14-16 in Orlando, FL, and suggest that these agents may be improving progression-free survival (PFS) and OS in men with prostate cancer.

“These new agents are revolutionizing how we treat advanced prostate cancer,” said E. David Crawford, MD, Professor of Surgery/Urology/Radiation Oncology at the University of Colorado, Denver, Colorado. “We now have more to offer the patients and there are fewer PSA failures. We are prolonging the lives of men with advanced prostate cancer for the first time in decades with the introduction of these newer agents. In the future, as we combine these agents, the benefit may be even more dramatic.”

Abiraterone Acetate plus Prednisone Shows Improved Survival Rates

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Abiraterone acetate (AA) is an inhibitor of CYP17 and blocks androgen biosynthesis.  In a phase 3, randomized, multicenter, placebo-controlled trial published in 2012, AA was shown to improve OS in patients with metastatic castration-resistant prostate cancer post-docetaxel.1 The COU-AA-302 updated interim analysis  included 1,088 patients randomly assigned 1:1 to receive either AA 1,000 mg or placebo once daily  plus prednisone 5mg twice daily.  The median follow-up was 27.1 months.

The latest findings from this study showed a statistically significant 47% reduction in the risk of radiographic PFS in the AA arm compared to the placebo control group.  The median radiographic PFS was 16.5 months in the AA group compared to 8.3 months in the control group.  While the treatment with AA plus prednisone resulted in an estimated 21% reduction in the risk of death, it did not reach the prespecified efficacy boundary.  The median OS was 35.3 months in the AA group compared to 30.1 months in the control group. 

“The study confirmed that abiraterone is effective in the pre-chemotherapy population and so this offers patients a new opportunity.  The side effects were low grade and it was well tolerated even at 2 years,” said study investigator Dana Rathkopf, MD, an assistant attending physician in the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center, New York, NY.  “Abiraterone doubled the time to radiographic progression-free survival compared to the prednisone control.  It favored overall survival and improved clinical benefits in terms of quality of life.”