Chicago, IL—Abiraterone acetate (Zytiga) delays disease progression when used with prednisone before chemotherapy in men with metastatic castration-resistant prostate cancer, said Charles J. Ryan, MD, Associate Professor of Clinical Med icine, Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, who reported a planned interim analysis of a phase 3 study at the 2012 meeting of the American Society of Clinical Oncology.
The finding represents a potential new use of abiraterone in prostate cancer; the drug is now approved only for men with metastatic castration- resistant prostate cancer in whom do cetaxel (Taxotere) chemo therapy has failed.
“These data merit consideration as providing a new standard approach in this highly prevalent population faced with an unmet medical need,” said Dr Ryan.
The trial included 1088 men with metastatic castration-resistant prostate cancer that was no longer responsive to hormonal therapy. It was conducted in 151 centers in North America, Europe, and Australia. The men were randomized to abiraterone plus prednisone or to placebo plus prednisone.
The trial was terminated early, with 43% of total events reported, given the favorable response on overall survival (OS) and progression-free survival (PFS) observed with abiraterone. At this point, the independent data monitoring committee recommended unblinding the study and offering the placebo recipients active treatment with abiraterone.
The median survival in this study was 14.8 months, with an improvement of 3.9 months over the prednisone control arm, “thus reflecting the advanced clinical stage of the population tested,” said Dr Ryan.
“A reality is that much of the life of a patient with metastatic castration-resistant prostate cancer is lived before chemotherapy, and, in fact, a large proportion of patients never receive it,” Dr Ryan stated in explaining the rationale for studying abiraterone in chemotherapy-naïve patients.
There was a 57% improvement in radiographic PFS, a coprimary end point, in men randomized to abiraterone. The median time to progression was 8.3 months in the control group, but the median time to PFS had not yet been reached in the abiraterone group at the time the trial was sus pended. “This represents an approx imate doubling of the radiographic progression-free survival,” he said.
The median survival in the prednisone control arm was 27.2 months, whereas the median survival had not yet been reached in the abiraterone arm, which conforms to a 25% improvement in survival, “a strong trend in favor of abiraterone,” Dr Ryan pointed out. This trend did not reach statistical significance because of the early termination of the trial.
Some 60.3% of the prednisone control group required additional therapies for prostate cancer, including docetaxel (the most common subsequent treatment) compared with only 44.3% of the abir aterone arm.
Abiraterone significantly delayed the time (by 31%) before patients needed opiates to control pain and the time (by 42%) to initiate chemotherapy.
Susan Halabi, PhD, Associate Professor of Biostatistics and Bioinformatics at Duke University Medical Center, Durham, NC, said that although the study represents the first to show activity of abiraterone in chemotherapy-naïve patients, she questioned early termination of the trial, before the difference in OS observed with abiraterone could achieve statistical significance.
Never theless, the survival benefit with abiraterone is most likely real, she said.—WK
