Data presented at the recent 35th European Society for Medical Oncology Congress in Milan, Italy, showed a significant survival advantage for men with advanced metastatic castration resistant prostate cancer (CRPC) who received abiraterone acetate compared with placebo. According to presenter Johann de Bono, MBBS, PhD, Institute of Cancer Research, Royal Marsden Hospital, London, United Kingdom, who was a lead investigator for the study, abiraterone improved median overall survival (OS) by nearly 4 months. He acknowledged that while this might not seem impressive, only 4 drugs in the history of prostate cancer had been found to improve OS. de Bono said men with metastatic CRPC typically “have a poor prognosis, with only about one in three alive 5 years after diagnosis” and that abiraterone had the potential to satisfy an unmet need in the care of patients with this disease.
The double-blind, phase III study was carried out across 147 centers in 13 countries, enrolling 1195 men with metastatic CRPC who had received prior treatment with docetaxel. The men were randomized to receive a daily 1000-mg dose of abiraterone plus 5 mg of the corticosteroid prednisone twice daily (n = 797) or the same dose of prednisone with placebo (n = 398). The primary endpoint of the study was OS; secondary endpoints included time to PSA progression, adiographic progression-free survival (PFS), and response measured as a PSA decline ≥50% from baseline.
Abiraterone was superior to placebo on all these endpoints. The oral agent reduced the risk of death by 35%, with a median OS of 14.8 months for the abiraterone group compared with 10.9 months for the placebo arm (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.54-0.77; P
<.0001). Median time to PSA progression as 10.2 months for patients taking abiraterone versus 6.6 months for those on placebo (HR, 0.58; 95% CI, 0.46-0.73; P
<.0001), and radiographic PFS was 5.6 months for the abiraterone group compared with 3.6 months for the placebo arm (HR, 0.67; 95% CI, 0.58-0.78; P
<.0001). Response in the abiraterone group reached 38% versus 10% in the placebo arm (P
Patients taking abiraterone had a higher incidence of adverse events compared with those on placebo. Overall, 30.5% of patients taking abiraterone experienced fluid retention versus 22.3% of patients given placebo. Hypokalemia (all grades) was also more common in the abiraterone arm compared with the placebo group (17.1% vs 8.4%, respectively). Liver testing abnormalities and cardiac events occurred at marginally higher rates in the abiraterone arm. “[Abiraterone] is well tolerated, and we now hope for the patient’s sake that we can make it widely available,” said de Bono.
In a discussion on abiraterone, Carsten Bokemeyer, MD, director of University Cancer Center, Hamburg, Germany, described it as “a true additional new treatment in prostate cancer.” He said, “The results of this study show that the drug adds to the range of treatment options for patients with advanced disease, with limited toxicity.”
The study leaves some questions unanswered, according to de Bono. Although benefit with abiraterone was consistent across all patient subgroups, researchers need to do molecular testing and other studies to determine why some patients fail to respond to the drug. In addition, studies need to look at the timing of hormone therapy and chemotherapy for men with metastatic CRPC, according to Bokemeyer. Another concern was the rapid PSA progression patients experienced when they were taken off abiraterone and how this might relate to survival. In a general session on emerging therapies for advanced prostate cancer, de Bono noted that 2 new drugs—sipuleucel T (Provenge) and cabazitaxel (Jevtana)— had recently been approved for men with advanced disease, and researchers would also have to determine whether combined or sequential therapy with abiraterone and these newly approved treatments might improve outcomes.
The Independent Data Monitoring Committee was so impressed with the interim analysis that it recommended the study be unblinded in September and patients in the placebo group be permitted to cross over to the abiraterone arm. “Once we knew that the drug could prolong life for many patients, it was ethically critical that we made it available to all patients on the trial,” de Bono explained. He is optimistic that it will eventually get approval and become standard therapy for men with advanced CRPC. Abiraterone has the potential to meet a significant unmet need, so this news will be incredibly important to prostate cancer patients and their families,” he said. Janssen Pharmaceutical, the maker of abiraterone, announced that it planned to file marketing applications in the United States and Europe before the start of 2011.