FDA approves label update for advanced PCa treatment

April 6, 2015

Final analysis of a phase III trial shows abiraterone acetate (ZYTIGA) plus prednisone extended overall survival compared to placebo plus prednisone in chemotherapy-naive men with mCRPC.

The FDA has approved a label update for abiraterone acetate (ZYTIGA) plus prednisone following publication of phase III trial data showing the combination therapy extended median overall survival compared to placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC).

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Data from the COU-AA-302 phase III trial were published in The Lancet Oncology (2015; 16:152-60). The study of the two regimens in 1,088 asymptomatic to mildly symptomatic men found that those receiving prednisone (5 mg, twice daily) plus abiraterone acetate (1,000 mg, once daily) experienced a median overall survival of 34.7 months (95% CI 32.7-36.8) compared to 30.3 months (95% CI 28.7-33.3) in men receiving a prednisone-placebo combination (p=.003).

Endpoints for the trial were radiographic progression-free survival and overall survival analyzed in the intention-to-treat population. Some 365 patients (67%) in the abiraterone group and 435 (80%) in the prednisone plus placebo alone group were given subsequent treatment with one or more approved chemotherapies.

During the course of the trial, 238 (44%) of the men receiving prednisone alone were moved to the combination therapy as an aspect of the crossover protocol (93 patients) or as a subsequent treatment (145 patients). The trial's median follow-up was 49.2 months.

The most common grade 3-4 side effects were cardiac disorders in 8% of the abiraterone group versus 4% of the prednisone-alone group, increased alanine aminotransferase in 6% of the abiraterone group compared to 1% in prednisone group, and hypertension in 5% of the abiraterone group versus 3% in the prednisone group.

"The statistically significant improvement in overall survival demonstrated in the final analysis and resulting label update help affirm the established efficacy, safety, and tolerability that physicians treating men with metastatic castration-resistant prostate cancer have seen with ZYTIGA," said lead investigator Charles J. Ryan, MD, of the University of California, San Francisco in a press release from Janssen Research & Development, LLC.

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Data from COU-AA-302 were also presented by Dr. Ryan at the Genitourinary Cancers Symposium in Orlando, FL. The final analysis showed that with the occurrence of 96% of the planned deaths (median follow-up: 49.2 months), abiraterone plus prednisone reduced the risk of death by 19% (p=.0033) compared with placebo and prednisone in this study of 1,088 men with asymptomatic or mildly symptomatic mCRPC. 

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After adjustment for crossover from placebo to abiraterone, the treatment effect was even more pronounced, with a 26% decrease (p<.0001) in the adjusted risk of death in the abiraterone group, Dr. Ryan said.

In commentary that accompanied publication of the trial, Ravi Madan, MD, and William L. Dahut, MD, of the National Cancer Institute, wrote that the shift of placebo-prednisone patients to abiraterone suggested that the latter regimen might have an even greater survival advantage than indicated by the trial's initial data (Lancet Oncol 2015; 16:119-21). They also noted that the abiraterone regimen significantly delayed the need for opiates (33.4 months [95% CI 30.2-39.8 months]) compared to prednisone (23.4 months [95% CI 20.3-27.5], HR 0.72 (95% CI 0.61-0.85, p<.0001).

The trial was sponsored by Janssen Research & Development. Dr. Ryan has received honoraria and travel, accommodations, and expenses remuneration from Janssen Pharmaceuticals, Inc.

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