On September 17, the U.S. Food and Drug Administration (FDA) approved apalutamide (Erleada) for patients with metastatic castration-sensitive prostate cancer. Apalutamide was initially approved by the FDA in 2018 for patients with nonmetastatic castration-resistant prostate cancer.
Efficacy was demonstrated in TITAN, a randomized, double-blind, placebo-controlled, multicenter phase III trial that enrolled 1,052 patients with metastatic castration-sensitive prostate cancer. Patients received either oral apalutamide at 240 mg daily or placebo. All patients received androgen-deprivation therapy consisting of either concomitant gonadotropin-releasing hormone analog or prior bilateral orchiectomy. Patients with both high- and low-volume disease were enrolled in the study.
Statistically significant improvements in both overall survival and radiographic progression-free survival were demonstrated. At the time of a prespecified interim analysis, the hazard ratio for overall survival was 0.67 (95% confidence interval [CI] = 0.51–0.89, P = .0053); median overall survival was not reached in either arm. The hazard ratio for the radiographic progression-free survival improvement was 0.48 (95% CI = 0.39–0.60, P < .0001). The median radiographic progression-free survival was not reached with apalutamide plus androgen-deprivation therapy and was 22.1 months with placebo plus ADT.
The most common adverse reactions (incidence ≥ 10%) for patients who received apalutamide were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture.
The recommended dose of apalutamide is 240 mg (four 60-mg tablets) orally once daily with or without food. Patients should also receive a gonadotropin-releasing hormone analog concurrently or should have had bilateral orchiectomy.