When patients with metastatic castration-resistant prostate cancer without prior chemotherapy were treated with abiraterone acetate plus prednisone, their risk of disease progression was reduced by almost half, and their risk of death was decreased by almost 20% compared with patients given prednisone alone, based on data from an interim analysis of the phase III trial COU-AA-302.
Treatment with both drugs also delayed times to opiate use and chemotherapy, was associated with improved quality of life measures, and remained safe and well tolerated, said Dr. Dana E. Rathkopf, the study’s lead author, who presented the results at the annual gastrointestinal cancers symposium sponsored by the American Society of Clinical Oncology. Results on quality of life measures were reported at last year’s European Society for Medical Oncology congress.
Dr. Dana E. Rathkopf
This was the third planned interim analysis for the randomized trial COU-AA-302, which is designed to evaluate the clinical benefit of abiraterone (Zytiga) and prednisone compared with prednisone alone in mildly symptomatic or asymptomatic patients with progressive metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy.
Similar to the findings at a previous interim analysis (43% of total overall survival events) conducted in December 2011, the third analysis (55% of overall survival events) continued to show that the radiographic progression-free survival (rPFS) in the abiraterone plus prednisone arm remained significant. Although overall survival continued to favor the abiraterone plus prednisone arm, it didn’t cross the boundary for significance.
"We may never get the answer to the question of whether prechemotherapy abiraterone can improve overall survival," commented Dr. William Oh, chief of hematology and medical oncology at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. "To me, that is okay as long as we still have evidence that [the drug has] meaningful value to patients" from a quality of life perspective.
For the COU-AA-302 trial, 1,088 patients were randomized to 1,000 mg/day of abiraterone plus 5 mg twice per day of prednisone or to the control arm of placebo plus prednisone. The treatment arms were evenly matched.
Coprimary endpoints were rPFS and overall survival. Secondary endpoints included time to opiate use, time to chemotherapy initiation, time to ECOG-PS (Eastern Cooperative Oncology Group–performance status) deterioration, and time to prostate-specific antigen (PSA) progression
At the third interim analysis, primary endpoints and all secondary endpoints favored the abiraterone and prednisone arm. The time to rPFS was doubled relative to the control arm (16.5 months and 8.3 months; HR = 0.53; P = .0001).
Overall survival was 35.3 months with abiraterone and prednisone versus 30.1 months with placebo and prednisone. The difference was not significantly different (HR = 0.79; P = .0151). Dr. Rathkopf and his colleagues pointed out that the median overall survival of 35.3 months is the longest reported for this mCRPC population.
Abiraterone plus prednisone also doubled the maximal decline in PSA compared with placebo and prednisone (11.1 months and 5.6 months; HR = 0.50; P = .0001). Prednisone is an active control therapy, as 29% of the patients in the control arm had a decline in PSA of greater than or equal to 50%, Dr. Rathkopf said.
The most common adverse event was fatigue. Beyond the 2 years since the study began, no new safety signals have emerged with abiraterone.
At a median follow-up of 27 months, 77% of the patients in the abiraterone and prednisone arm and 89% in the placebo and prednisone arm had discontinued therapy, mainly because of disease progression.
Dr. Rathkopf said he had no financial relationships to disclose. Dr. Oh has been a consultant or adviser to several drug makers including Janssen Biotech, the maker of Zytiga.