FDA Approves Zytiga Label Update for Use in Chemo-Naive Men with Metastatic Prostate Cancer

The Food and Drug Administration (FDA) has updated the label for Zytiga (abiraterone acetate) plus prednisone to include data from the final analysis of the phase 3 COU-AA-302 study, which detailed a significant prolongation in overall survival (OS) for Zytiga 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 Zytiga versus 30.3 months with placebo. Following treatment on the trial, 67 percent of patients in the Zytiga arm compared with 80 percent in the placebo arm received subsequent therapy. The final analysis was conducted following 96 percent 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 Ryan, 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 Zytiga 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 Zytiga plus prednisone or prednisone and placebo. The co-primary outcome measures were rPFS and OS.

Following the unblinding of the study, 44 percent of patients enrolled in the placebo arm crossed over to receive Zytiga. At the time of the final analysis, 92 percent of patients in the Zytiga arm and 100 percent 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 Zytiga versus 23.4 months with placebo. The iterative parameter estimate adjusted reduction in the risk of death with abiraterone was 26 percent versus placebo. When adjusting for baseline prognostic factors, Zytiga led to a 21 percent reduction in the risk of death.

The most common grade 3/4 adverse events associated with Zytiga versus placebo were cardiac disorders, increased alanine aminotransferase, and hypertension.

The FDA initially approved Zytiga 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 Zytiga compared with 11.2 months with placebo.

"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, 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 Zytiga as a treatment for men with CRPC. These investigations are looking at the agent in combination with the PARP inhibitors Lynparza (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.