Abiraterone Delays Progression in Patients with Chemotherapy-Naïve CRPC

In patients with asymptomatic or mildly symptomatic chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate (AA) plus prednisone produced a statistically significant benefit in radiographic progression-free survival (rPFS) over placebo plus prednisone, according to a planned interim analysis of a phase III study.

AA plus prednisone delayed disease progression, increased survival, and extended time with minimal or no symptoms, said Charles J. Ryan, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. In addition, no important new safety signals were seen in the randomized, multicenter COUAA- 302 study, added Dr. Ryan, who presented the results of the interim analysis at a Clinical Science Symposium on Saturday (Abstract LBA4518).

At the second planned interim analysis of the COU-AA-302 study, with 43% of total events reported, the independent data monitoring committee concluded that the co-primary endpoints of overall survival (OS) and rPFS and secondary endpoints all favored the AA arm and unanimously recommended unblinding the study and crossing patients over from placebo to AA treatment, Dr. Ryan said.

“The results of this study suggest in aggregate that the objectives of therapy development in this disease state have been met, as treatment with abiraterone acetate proved favorable for patients across a full spectrum of clinical outcomes,” he said. “These data merit consideration as providing a new standard approach in this highly prevalent patient population faced with an unmet medical need.”

Study Design Rationale

AA is routinely administered with prednisone to optimize its safety profile, Dr. Ryan noted. AA plus prednisone previously demonstrated a benefit in OS over a prednisone control in patients with previous chemotherapy exposure, and these study results were used to support the regulatory approval of the drug in the United States and other countries.

“However, a reality is that much of the life of a patient with mCRPC is lived before chemotherapy, and in fact a large proportion of patients never receive it,” he said.

The natural history of progressive mCRPC can be prolonged, and can appear over a period of years. Therefore, several hallmarks of disease progression (time to opiate use as a surrogate for cancer-related pain, time to initiation of chemotherapy, time to Eastern Cooperative Oncology Group performance status deterioration, time to PSA progression) were used as secondary endpoints, to provide “a comprehensive assessment of the magnitude of the clinical benefit conferred by AA,” Dr. Ryan said. “Therapy with AA delayed, to a clinically significant degree, the onset of these meaningful events,” he said.

The co-primary endpoint included progressive disease as determined by bone scan with blinded review by a central radiologist, progressive disease as determined by soft tissue lesions seen on computed tomography or magnetic resonance imaging, or death from any cause. Despite longer treatment with AA than in the prior study in patients with previous chemotherapy, no new safety signals were seen in the trial.

Statistical Analysis

Discussant Susan Halabi, PhD, of Duke University Medical Center, said that the trial represents a paradigm shift, as it is the first study to show activity of AA in chemotherapy-naïve patients.

However, she questioned the wisdom of stopping the trial early, before a statistically significant benefit in OS was shown.

“The decision to stop a trial early is complex, requiring a combination of both statistical and clinical judgment,” she said. “Stopping a trial too early may fail to persuade others to change medical practice.”