The FDA has approved a new indication for abiraterone acetate in combination with prednisone for the treatment of patients with metastatic high-risk castration-sensitive prostate cancer (CSPC). The approval is based on phase III data from the pivotal LATITUDE clinical trial, which found that in patients with metastatic high-risk CSPC, abiraterone acetate in combination with prednisone reduced the risk of death by 38 percent compared to placebos.
"LATITUDE was a large global trial which produced impressive and clinically significant results in overall survival," said Karim Fizazi, MD, PhD, Principal Investigator and Head of the Medical Oncology Department at Institute Gustave Roussy, Villejuif, France. "With today's approval, abiraterone acetate plus prednisone could become a standard of care for patients with metastatic high-risk castration-sensitive prostate cancer."
LATITUDE was a multinational, multicenter, randomized, double-blind, placebo-controlled clinical trial that examined the use of abiraterone acetate 1,000 mg once daily in combination with prednisone 5 mg once daily, compared to placebos in patients with newly diagnosed, metastatic high-risk CSPC, who had not received prior cytotoxic chemotherapy.
The study enrolled 1,199 patients and was conducted at 235 sites in 34 countries in Europe, Asia-Pacific, Latin America, and Canada. A total number of 597 patients were randomized to receive abiraterone acetate plus prednisone, while 602 patients were randomized to receive placebo. All the patients received a gonadotropin-releasing hormone (GnRH) analog or had prior bilateral orchiectomy. The study data were presented at the plenary session of the 2017 ASCO Annual Meeting, and simultaneously published in The New England Journal of Medicine (2017; 377:352-360).
The study showed abiraterone acetate in combination with prednisone reduced the risk of death by 38 percent compared to placebos (median OS not estimable vs. 34.7 months, respectively; hazard ratio (HR)=0.62; 95% confidence interval (CI): [0.51, 0.76], p<0.0001). Additional data demonstrated statistically significant delay in time to initiation of chemotherapy for patients in the abiraterone acetate arm compared to those in the placebo arm (median time to initiation of chemotherapy not reached vs. 38.9 months, respectively; HR=0.44; 95% CI: [0.35, 0.56], p < 0.0001).
High-risk disease was defined as having at least two of three risk factors at baseline: a total Gleason score of ≥8, presence of ≥3 lesions on bone scan, and evidence of measurable visceral metastases. Patients with significant cardiac, adrenal, or hepatic dysfunction were excluded. The median duration of treatment with abiraterone acetate and prednisone was 24 months.
The most common adverse reactions (≥10%) that occurred more commonly (>2%) in the abiraterone acetate arm from an analysis of pooled safety data were fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache.
Metastatic castration-sensitive prostate cancer (CSPC), also referred to as metastatic hormone-sensitive prostate cancer (HSPC) in literature, refers to prostate cancer that still responds to testosterone suppression therapy. Patients with newly-diagnosed metastatic disease and high-risk disease characteristics tend to have a poorer prognosis.
Since its first approval in the U.S. in 2011, abiraterone acetate has been approved in combination with prednisone or prednisolone, in 105 countries. More than 330,000 patients worldwide, including 113,000 in the U.S., have received treatment with it, and it was the number one prescribed oral medication in the U.S. for patients with metastatic CRPC in 2016.