Abiraterone acetate (Zytiga?; Janssen Research & Development, LLC) is an androgen biosynthesis inhibitor that inhibits CYP17 and improves overall survival (OS) in post-docetaxel metastatic castration-resistant prostate cancer (mCRPC).

The primary objective of COU-AA-302, a Phase III, randomized, placebo-controlled study, was to compare clinical benefit of abiraterone acetate + prednisone (P) vs placebo (PL) + P in chemo-naive, asymptomatic/mildly symptomatic mCRPC patients. Efficacy data for was published this week online in the New England Journal of Medicine(NEJM).

Trial results
The data from 1,088 asymptomatic or mildly symptomatic patients with showed statistically significant improvements in radiographic progression-free survival and other prospectively defined efficacy endpoints compared to placebo plus prednisone (control arm), including time to initiation of cytotoxic chemotherapy and time to initiation of opioid use for cancer pain. The results also showed longer overall survival, the co-primary endpoint, in the abiraterone acetate arm compared to the control arm.

Expanded indication
This study was the basis of Monday’s U.S. Food and Drug Administration (FDA) approval of an expanded indication of abiraterone acetate , in combination with prednisone, in metastatic castration-resistant prostate cancer. Previously, abiraterone acetate with prednisone had only been approved for use in men with mCRPC after chemotherapy.

Earlier use
“These results, now published in a major peer-reviewed medical journal, highlight the value of earlier use of abiraterone acetate in treating metastatic castration-resistant prostate cancer and advance our understanding of the role of its mechanism of action,” said Charles J. Ryan, M.D., lead investigator of the study and associate professor of clinical medicine at the UCSF Helen Diller Family Comprehensive Cancer Center.

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“This certainly has been an exciting week,” said Michael L. Meyers, M.D., Ph.D., vice president, compound development team leader, abiraterone acetate . “But more importantly, these milestones mean men living with this devastating disease have a new treatment option before chemotherapy.”

Worldwide approval
Since its first approval in the U.S. in 2011, abiraterone acetate has been approved in more than 65 countries. More than 40,000 men worldwide have received treatment with it, and it is quickly becoming one of the cornerstones of treatment for mCRPC.

Adverse events (AEs)
Fatigue, arthralgia (joint pain) and peripheral edema (foot, leg, and ankle swelling) were among the adverse events (AEs) reported more frequently in the abiraterone acetate arm compared to the control arm. Patients in the abiraterone acetate arm of the study experienced more grade 3 and grade 4 adverse events than those in the control arm, more serious AEs and more adverse events with an outcome of death. Grade 3 or 4 adverse events classified as liver toxicity, consisting primarily of reversible elevations in liver transaminase enzymes, were reported in both arms. No patient in either treatment group died from liver toxicity-related adverse events.

For more information:
– Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy. N Engl J Med. 2012 Dec 10. [Epub ahead of print] [Full text][PubMed]
– Ryan CJ, Smith MR, De Bono JS, Molina A, Logothetis C, De Souza PL, Fizazi K, et al. Interim analysis (IA) results of COU-AA-302, a randomized, phase III study of abiraterone acetate (AA) in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 30, 2012 (suppl; abstr LBA4518)

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