A combination regimen plus androgen-deprivation therapy prolongs overall survival (OS) and radiographic progression-free survival (PFS) in newly diagnosed patients with metastatic, castration-sensitive prostate cancer, according to a recent study published in the New England Journal of Medicine (July 27, 2017;377:352-360).
Abiraterone acetate in combination with prednisone has demonstrated effectiveness in patients with metastatic, castration-resistant prostate cancer who have not received prior chemotherapy or in those who have received previous docetaxel. Including androgen-deprivation therapy in this regimen has been shown to reduce tumor burden in men with high-risk, localized prostate cancer who are receiving neoadjuvant therapy.
Karim Fizazi, MD, PhD, and colleagues conducted a study to further evaluate the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer. The double-blind, placebo-controlled, phase III trial randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250 mg tablets) plus prednisone (5 mg daily) or androgen-deprivation therapy plus dual placebos.
Primary endpoints included OS and radiographic PFS.
After a mean follow-up of 30.4 months, 406 patients had died. The median OS was significantly longer in the abiraterone group compared with the placebo group (not reached vs 34.7 months, respectively; HR for death, 0.62; 95% CI, 0.51-0.76; P < .001). Median length of radiographic PFS was 33.0 months in the abiraterone group and 14.8 months in the placebo group (HR, 0.47; 95% CI, 0.39-0.55; P < .001).
Due to considerably improved outcomes in all secondary endpoints in the abiraterone group (ie time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, prostate-specific antigen progression, and next symptomatic skeletal events), the independent data and safety monitoring committee unanimously recommended the trial be unblinded and crossover be permitted for patients in the placebo group to receive abiraterone.
Researchers acknowledged that grade 3-4 hypokalemia and hypertension were higher in the abiraterone group.
Researchers concluded that, “the addition of abiraterone plus prednisone to androgen-deprivation therapy was associated with longer OS and longer radiographic PFS than was androgen-deprivation therapy alone.”—Zachary Bessette