FDA Updates Label for Abiraterone in mCRPC

Charles J. Ryan, MD

Charles J. Ryan, MD

The FDA has updated the label for abiraterone acetate (Zytiga) plus prednisone to include data from the final analysis of the phase III COU-AA-302 study. COU-AA-302 showed a significant prolongation in overall survival (OS) for abiraterone versus placebo in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC).

At the final 49.2-month analysis of the COU-AA-302 study, the median OS was 34.7 months with abiraterone versus 30.3 months with placebo (HR = 0.81; 95% CI, 0.70-0.93;P= .0033). Following treatment on the trial, 67% of patients in the abiraterone arm compared with 80% in the placebo arm received subsequent therapy. The final analysis was conducted following 96% of prespecified death events.

"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," COU-AA-302 lead investigator Charles J. Ryan, MD, professor of Clinical Medicine, Urology at the University of California, San Francisco, said in a statement. "Representing a median follow-up of four years, this analysis adds to the robust body of clinical data supporting Zytiga as an important treatment option for men with metastatic castration-resistant prostate cancer."

The FDA approved abiraterone as a treatment for chemotherapy-naive men with mCRPC in December 2012. The approval was based on improvement in median radiographic progression-free survival (rPFS), time-to-opiate, and time-to-cytotoxic chemotherapy in patients treated with abiraterone. At the time, OS data were immature.

In the trial, 1088 patients were randomized in a 1:1 ratio to abiraterone plus prednisone (n = 546) or prednisone and placebo (n = 542). Abiraterone was administered at 1000 milligram once daily and prednisone was administered at 5 mg twice daily. The co-primary outcome measures were rPFS and OS.

Following the unblinding of the study, 44% of patients enrolled in the placebo arm crossed over to receive abiraterone. At the time of the final analysis, 92% of patients in the abiraterone acetate arm and 100% in the placebo arm discontinued therapy. Disease progression was the primary cause of discontinuation in both arms.

The median time to opiate use was 33.4 months with abiraterone versus 23.4 months with placebo (HR = 0.72; 95% CI, 0.61-0.85;P= .0001). The iterative parameter estimate adjusted reduction in the risk of death with abiraterone was 26% versus placebo (P<.0001). When adjusting for baseline prognostic factors, abiraterone led to a 21% reduction in the risk of death (P=.0013).

The most common grade 3/4 adverse events associated with abiraterone versus placebo were cardiac disorders (8% vs 4%), increased alanine aminotransferase (6% vs <1%], and hypertension (5% vs 3%).

The FDA initially approved abiraterone in 2011 as a treatment for men with mCRPC following prior docetaxel, based on a 4.6-month extension in OS seen with the androgen synthesis inhibitor. The median OS seen in this trial, labeled COU-AA-301, was 15.8 months with abiraterone compared with 11.2 months with placebo (HR = 0.740; 95% CI, 0.638-0.859).

"Since its launch in 2011, Zytiga has helped change the treatment paradigm for metastatic castration-resistant prostate cancer, treating more than 150,000 men worldwide," Cynthia Guzzo, MD, vice president, Medical Affairs, Janssen Scientific Affairs, LLC, the company developing the drug, said in a statement. "This label update marks an exciting milestone for Zytiga and Janssen as we continue to focus on our commitment to patient care in the prostate cancer treatment space."

A number of ongoing clinical trials continue to assess abiraterone as a treatment for men with CRPC. These investigations are looking at the agent in combination with the PARP inhibitors olaparib or veliparib, with the radiopharmaceutical radium-223, and in various sequences with other approved agents. The agent is also being explored as a potential treatment for patients with breast cancer.