Abiraterone Acetate Significantly Improved Overall Survival for Patients with Metastatic Advanced Prostate Cancer
Toronto, ON, October 12, 2010 – Results from a pre-specified interim analysis of a randomized, placebo-controlled Phase 3 study, COU-AA-301, demonstrate that patients treated with the investigational agent abiraterone acetate plus low dose prednisone/prednisolone showed a significant improvement in overall survival compared to patients treated with prednisone/prednisolone plus placebo. This study included 1,195 patients worldwide, including 154 Canadian patients, with metastatic advanced prostate cancer (also referred to as castration-resistant prostate cancer, or CRPC) previously treated with one or two chemotherapy regimens, at least one of which contained docetaxel.
The results of this randomized, placebo-controlled study were shared during a late-breaking presentation at the Presidential Symposium at the 35th Annual European Society for Medical Oncology (ESMO) Congress.
Treatment with abiraterone acetate resulted in a 35 per cent reduction in the risk of death (HR=0.65; 95 per cent CI: 0.54, 0.77; p<0.0001) and a 36 per cent increase in median survival (14.8 months vs. 10.9 months) compared with placebo.
Patients who received abiraterone acetate and low dose prednisone/prednisolone also showed significant improvements in secondary study endpoints when compared to the prednisone/prednisolone plus placebo group: time to PSA progression (TTPP) [median 10.2 months for abiraterone acetate vs. 6.6 months for placebo, HR=0.58 (95 per cent CI: 0.46, 0.73); p<0.0001] and an increase in radiographic progression free survival (rPFS) [median 5.6 months for abiraterone acetate vs. 3.6 months for placebo, HR=0.67 (95 per cent CI: 0.58, 0.78); p<0.0001]. Total PSA response, defined as greater than or equal to a 50 per cent decrease from baseline, was achieved in 38 per cent of patients treated with abiraterone acetate vs. 10 per cent in the prednisone/prednisolone plus placebo group [p<0.0001].
Patients in the abiraterone acetate group experienced more mineralocorticoid-related adverse events than those in the prednisone/prednisolone plus placebo group. The most frequent adverse events were fluid retention (30.5 per cent vs. 22.3 per cent) and hypokalemia (17.1 per cent vs. 8.4 per cent). Grade 3/4 hypokalemia and hypertension were more frequent in the abiraterone acetate arm than in the placebo arm (3.8 per cent vs. 0.8 per cent and 1.3 per cent vs. 0.3 per cent, respectively). Liver function test abnormalities were observed in 10.4 per cent of abiraterone acetate treated patients compared to 8.1 per cent in the prednisone/prednisolone plus placebo group. Cardiac disorders were observed in 12.5 per cent of abiraterone acetate patients vs. 9.4 per cent of patients who received placebo. Mechanism-based adverse events were amenable to medical management and distinct from adverse events commonly associated with cytotoxic chemotherapy.
“Abiraterone has the potential to meet a significant unmet need so this news will be incredibly important to prostate cancer patients and their families," said Johann S. de Bono, MD, FRCP, MSc, PhD, The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, one of the lead COU-AA-301 investigators. “We are very pleased with the definitive results of this rigorous study, which show that abiraterone acetate may extend survival for men with metastatic advanced prostate cancer that progressed after treatment with docetaxel.”
Janssen-Ortho Inc. will have the marketing rights to abiraterone acetate in Canada. In Canada, abiraterone acetate has not received marketing authorization and is for investigational use only. Based on the positive results of the Phase 3 study, COU-AA-301, Janssen is planning for marketing applications with regulatory authorities worldwide.
“It is estimated that one in seven Canadian men will develop prostate cancer in his lifetime and in 2010 an estimated 4,300 men in Canada will die because of it,” said Dr. Kim Chi, Medical Oncologist at the BC Cancer Agency and The Vancouver Prostate Centre and COU-AA-301 trial investigator. “The study results are important because they demonstrate a much needed new advancement in the treatment of metastatic, castration-resistant prostate cancer – a stage of the disease that currently has few treatment options and a high mortality rate.”
A program that provides early access to abiraterone acetate for eligible patients is expected to be opened in the United States in October and will be opened in sites outside the United States in the following months, with the timing of the program contingent on local health authority and ethics committee approvals.
“The results of this abiraterone acetate Phase 3 study in patients with metastatic advanced prostate cancer bring us closer to achieving our goal of developing extraordinary preventive, diagnostic and therapeutic solutions based on our tumour microenvironment strategy,” said William N. Hait, MD, PhD, Global Therapeutic Head, Oncology, Ortho Biotech Oncology Research & Development. “We believe that abiraterone acetate is an important medical advance, and we look forward to further developing oncology therapeutic options that may impact patients’ lives.”
Ortho Biotech Oncology Research & Development, a unit of Cougar Biotechnology, Inc., previously announced that the Independent Data Monitoring Committee recommended unblinding this Phase 3 study after a pre-specified interim analysis demonstrated a statistically significant improvement in median overall survival and an acceptable safety profile. The IDMC also recommended that patients in the prednisone/prednisolone plus placebo group be offered treatment with abiraterone acetate.
(Source: http://www.jnj.com/connect/news/all/Abiraterone-Acetate-Significantly-Improved-Overall-Survival-Patients-with-Metastatic-Advanced-Prostate-Cancer)
