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 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 today at the 35th Annual European Society for Medical Oncology (ESMO) Congress.
Treatment with abiraterone acetate resulted in a 35 percent reduction in the risk of death>
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,>
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 percent vs. 22.3 percent) and hypokalemia (17.1 percent vs. 8.4 percent). Grade 3/4 hypokalemia and hypertension were more frequent in the abiraterone acetate arm than in the placebo arm (3.8 percent vs. 0.8 percent and 1.3 percent vs. 0.3 percent, respectively). Liver function test abnormalities were observed in 10.4 percent of abiraterone acetate treated patients compared to 8.1 percent in the prednisone/prednisolone plus placebo group. Cardiac disorders were observed in 12.5 percent of abiraterone acetate patients vs. 9.4 percent 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 acetate 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."
The Company plans to file marketing applications for abiraterone acetate with regulatory authorities in the U.S. and Europe by the end of the year. Applications in the rest of the world will follow, according to local regulatory requirements. If approved, abiraterone acetate will be commercialized and distributed by Centocor Ortho Biotech Inc. in the U.S. and by Janssen Pharmaceutical Companies in all other countries around the world.
"Globally, prostate cancer, the fifth most common cancer overall, is a significant public health problem," said Howard I. Scher, MD, Memorial Sloan-Kettering Cancer Center, one of the lead COU-AA-301 investigators. "These results are important because men with progressive metastatic, castration-resistant prostate cancer often have a poor prognosis and currently have few treatment options."
A program that provides early access to abiraterone acetate for eligible patients is expected to be opened in the U.S. in October and will be opened in sites outside the U.S. 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 tumor 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.
Ortho Biotech Oncology Research & Development