On April 28, the FDA announced the approval of abiraterone acetate (Zytiga) in conjunction with a steroid, prednisone(Drug information on prednisone), as treatment for late-stage (metastatic) castration-resistant prostate cancer patients who have received prior docetaxel(Drug information on docetaxel). Zytiga is expected to be used after sipuleucel-T (Provenge), a personalized immunotherapy that is indicated for asymptomatic late-stage or asymptomatic hormone-refractory prostate cancer. Johnson and Johnson, the manufacturer of abiraterone acetate, also has ongoing clinical trials for treatment-naïve prostate cancer patients. The results of those trials are expected in 2012.
The approval comes earlier than the expected June, 2011 decision date. Abiraterone acetate was reviewed by the FDA under the expedited six-month review program, targeted for major advances in treatments or for indications for which there is currently no adequate therapy.
“Zytiga prolonged the lives of men with late-stage prostate cancer who had received prior treatments and had few available therapeutic options,” said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research.
Abiraterone acetate is a second-line oral, hormone therapy. The treatment decreases the production of testosterone by targeting the enzyme cytochrome P450 17A1 (CYP17A1), which is involved in the metabolism of an intermediate to testosterone. In prostate cancer, testosterone normally stimulates prostate tumors to continue to grow.
The phase III two-arm trial of 1,195 patients who received prior docetaxel chemotherapy was designed to show overall survival. Patients received either the experimental treatment or placebo once daily in combination with prednisone two times daily. Patients who received abiraterone acetate showed a 3.9-month survival benefit compare to those on placebo. Patients who received the abiretarone acetate and prednisone combination had a median overall survival of 14.8 months, compared to 10.9 months for patients receiving the placebo and prednisone combination.
The most frequent side effect of treatment was fluid retention, usually in the legs and feet, seen in roughly one-third of men in the treatment arm of the trial. Other side effects included joint swelling or discomfort, low levels of potassium in the blood (hypokalemia), muscle discomfort, hot flashes, diarrhea, urinary tract infection, cough, high blood pressure, heartbeat disorders, urinary frequency, increased nighttime urination, upset stomach or indigestion, and upper respiratory tract infection.
“As a clinician, I believe the efficacy and safety profile of abiraterone acetate, as well as its oral, once-daily formulation, will help address the important need for additional therapeutic choices for men living with this serious disease,” Howard Scher, MD, of Memorial Sloan-Kettering Cancer Center in New York, says in the company’s news release.