(ChemotherapyAdvisor) – Abiraterone acetate (AA) blockade of extragonadal androgen synthesis prolongs overall survival (OS) among patients with metastatic castration-resistant prostate cancer (mCRPC) who have not undergone prior chemotherapy, according to an updated interim analysis of data from a randomized phase 3 clinical trial reported at the 4th annual Genitourinary Cancers Symposium in Orlando, FL.
“Median OS for AA (35.3 months) is the longest reported for this mCRPC population,” reported lead author Dana E. Rathkopf, MD, at Memorial Sloan-Kettering Cancer Center, New York, NY. “Secondary endpoints were clinically and statistically significant, and the safety profile despite longer exposure remains favorable. Targeting extragonadal androgen synthesis reduces morbidity associated with disease progression in mCRPC patients without prior chemotherapy.”
At a median follow-up of 27.1 months, OS, radiographic progression-free survival (rPFS) and secondary endpoints “all favored the AA arm,” Dr. Rathkopf and colleagues reported. Improved rPFS “remained statistically significant” with a risk reduction of 47%, they noted.
Hazard ratios (HRs) for rPFS and OS were 0.53 (95% CI: 0.45-0.62; P<0.0001) and 0.79 (95% CI: 0.66-0.96; P=0.0151), respectively, the researchers reported. Times to chemotherapy initiation, Eastern Cooperative Oncology Group (ECOG) performance status deterioration, and prostate-specific antigen progression were also superior among patients in the AA study arm (HRs, 0.61, 0.83 and 0.50, respectively; P<0.0001, P = 0.0052, and P<0.0001, respectively).
AA inhibits CYP17, blocks androgen biosynthesis, and has previously been shown to improve OS in mCRPC patients previously treated with docetaxel. The new pre-specified updated interim analysis for the COU-AA-302 trial (NCT00887198) compared the clinical benefits of AA compared with prednisone and placebo after 55% of total OS events among asymptomatic and mildly symptomatic patients with mCRPC who had not received previous chemotherapy, Dr. Rathkopf and colleagues reported. A total of 1,088 patients had been stratified by ECOG performance status (0 vs. 1) and randomized 1:1 to receive AA (1,000 mg plus prednisone 5 mg orally, twice daily) or placebo plus prednisone.
Grade 3/4 adverse events in the AA and placebo arm included hypertension (4.2% vs. 3.1%, respectively), hypokalemia (2.6% vs. 1.9%, respectively), elevated ALT (5.5% vs. 0.7%, respectively), and elevated AST (3.1% vs. 0.9%, respectively), the researchers reported.
“Risk of death decreased by 21% but did not reach pre-specified efficacy boundary,” they noted.
The 2013 Genitourinary Cancers Symposium is co-sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO).
Clinical trial information: NCT00887198.