FDA Approves Apalutamide for Prostate Cancer

September 18, 2019

Apalutamide was initially approved in 2018 for patients with non-metastatic castration-resistant prostate cancer; the recent approval is for patients with metastatic castration-sensitive prostate cancer.

The US Food and Drug Administration approved the use of apalutamide for patients with with metastatic castration-sensitive prostate cancer, according to a Sept. 18 release from the agency. The drug was previously approved in 2018 for patients with non-metastatic castration-resistant prostate cancer.

The recommended dose is 240 mg (four 60 mg tablets) orally once a day. Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

Approval process

Efficacy was demonstrated in the TITAN trial, a randomized, double-blind, placebo-controlled, multi-center clinical trial enrolling 1,052 patients with metastatic castration-sensitive prostate cancer. Patients received either the recommended apalutamide dosage or a placebo. All patients received androgen deprivation therapy-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 major efficacy outcomes of overall survival (OS) and radiographic progression-free survival (rPFS) were demonstrated. At the time of a pre-specified interim analysis, the hazard ratio for OS was 0.67 (95% CI: 0.51, 0.89; P=0.0053); however, median OS was not reached in either arm. The hazard ratio for the rPFS improvement was 0.48 (95% CI: 0.39, 0.60; p<0.0001). The median rPFS was not reached for the apalutamide plus ADT arm, and was 22.1 months for the placebo plus ADT arm.

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.