April 28, 2011
The US Food and Drug Administration (FDA) has approved abiraterone acetate (Zytiga, Cougar Biotechnology) in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer in men who have received prior … docetaxel chemotherapy.
The application was reviewed under the FDA’s priority review program, and the new oral agent is being approved ahead of the product’s June 20, 2011, regulatory goal date, according to the FDA.
In the pivotal COU-AA-301 trial, patients who received abiraterone acetate plus prednisone had a median overall survival duration of 14.8 months, compared with 10.9 months for patients receiving prednisone plus placebo. The difference was statistically significant.
Abiraterone treatment also resulted in significant differences between the 2 treatment groups for all the COU-AA-301 trial’s secondary endpoints, including time to prostate-specific antigen (PSA) progression, radiographic progression-free survival, and PSA response rate.
These results and the survival data were presented this year at the 35th European Society for Medical Oncology (ESMO) Congress.
Johann de Bono, MBBS, PhD (London): “While 3.9 months may not seem like much, in the history of prostate cancer, only 4 drugs have ever shown a survival benefit,” he noted at ESMO.
Abiraterone works by decreasing the production of testosterone, which stimulates prostate cancer cell growth. In the COU-AA-301 study, Dr. de Bono and colleagues randomly assigned 1195 patients with castration-resistant metastatic prostate cancer who had been previously treated with docetaxel to receive abiraterone, 1000 mg, plus prednisone, 5 mg, twice daily (n = 797) or placebo plus prednisone (n = 398) at 147 centers in 13 countries.
Liver function test abnormalities were reported in 10.4% of the patients who received the investigational agent compared with 8.1% in the placebo group. Cardiac problems were also more common in the abiraterone group compared with placebo, at 12.5% vs 9.4%.However, overall, Dr. de Bono believes that the drug is not terribly toxic. “It is an oral agent and does not have the toxicity of chemotherapy, and it is well tolerated in my experience,” he said at ESMO.
In addition to the newly approved abiraterone, 2 other new agents have been approved for men with advanced prostate cancer in the past year. Sipuleucel-T (Provenge, Dendreon) is an immunotherapy indicated for asymptomatic or minimally symptomatic men with castration-resistant metastatic prostate cancer. It improved overall survival duration by a median of 4.1 months compared with survival in a control group.
Another new second-line option in this setting — cabazitaxel (Jevtana, Sanofi-Aventis) — has also been shown in a phase 3 trial to prolong overall survival; median survival duration was 15.1 months in the cabazitaxel group and 12.7 months in the mitoxantrone group.