Treatment options for advanced prostate cancer have expanded again with Food and Drug Administration approval of abiraterone acetate for use in men who have not yet received chemotherapy for late-stage castration-resistant disease.
The agency initially approved abiraterone (Zytiga) in April 2011 for treatment of metastatic castration-resistant prostate cancer that had previously been treated with chemotherapy containing docetaxel (Taxotere) with prednisone.
The new indication, announced Dec. 10, endorses earlier treatment of patients with metastatic castration-resistant prostate cancer at the same oral dose of 1,000 mg twice daily in combination with 5 mg of prednisone.
European regulatory authorities also have expressed support for an expanded indication there, according to Janssen Biotech Inc., which markets abiraterone.
Opens Door for Broader Use
Abiraterone is part of an arsenal of recently approved prostate cancer therapies that are transforming care of men with advanced malignancy. These include the new immunotherapy sipuleucel-T (Provenge), cabazitaxel (Jevtana), and enzalutamide (Xtandi) for the disease itself – and denosumab (Prolia, Xgeva) for related bone-related indications.
The expanded approval for abiraterone "will allow many more men to benefit from this exciting new agent," Dr. Judd Moul, director of the Duke Prostate Center at Duke University, Durham, N.C., said in an interview.
Since it was approved in 2011 for use after chemotherapy, abiraterone has been used extensively, mostly by medical oncologists, he noted. In this setting, there was about a 4-month average survival benefit, compared with placebo.
Dr. Judd Moul
The survival benefit was "even more robust" in the prechemotherapy setting in men with advanced prostate cancer becoming resistant to traditional hormonal therapy, such as leuprolide and oral antiandrogens, he added.
The approval also will "open up the door for more urologists to gain experience using the drug, since urologists commonly treat men with advanced prostate cancer before they start chemotherapy," predicted Dr. Moul, the James H. Semans, M.D. professor of surgery at Duke.
Expanded Indication Followed Priority Review
The FDA considered the expanded indication in a priority review, completed in 6 months instead of the standard 12-month review and used for drugs that "may offer major advances in treatment or provide a treatment when no adequate therapy exists," according to the agency.
Abiraterone is an androgen suppressant. It decreases production of testosterone by inhibiting CYP17A1, an enzyme that is expressed in testicular, adrenal, and prostatic tumor tissues and needed for androgen biosynthesis.
The new approval was based on the results of the placebo-controlled international COU-AA-302 trial (N. Engl. J. Med. Dec. 10 [doi:10.1056/NEJMoa1209096]).
Investigators randomized 1,088 men who had late-stage castration-resistant prostate cancer and had not yet received chemotherapy. The men were randomized to treatment with abiraterone (1,000 mg/day) and prednisone (5 mg twice a day) or prednisone alone.
Median overall survival was 35.3 months among those who received abiraterone, compared with 30.1 months among those on placebo, according to the FDA statement. The median radiographic progression-free survival was 8.3 months among those on placebo but had not yet been reached among those on abiraterone at the time the analysis was conducted.
Overall survival and radiographic progression-free survival were the coprimary end points of the trial.
Treatment with abiraterone also was associated with significant improvements in the median time to opiate use for cancer pain (not reached with abiraterone vs. 23.7 months with placebo) and initiation of cytotoxic chemotherapy (25.2 months with abiraterone vs. 16.8 months with placebo), according to the prescribing information.
Among the most common side effects reported among those on abiraterone were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and bruising.