On December 16, the U.S. Food and Drug Administration (FDA) approved enzalutamide (Xtandi) for patients with metastatic castration-sensitive prostate cancer. The FDA previously approved enzalutamide for patients with castration-resistant prostate cancer.
Efficacy was investigated in ARCHES, a trial that enrolled 1,150 patients with metastatic castration-sensitive prostate cancer. Patients were randomly assigned 1:1 to receive either 160 mg of enzalutamide orally once daily (n = 574) or placebo orally once daily (n = 576). All patients received a GnRH analog or had a prior bilateral orchiectomy.
The main efficacy outcome measure was radiographic progression-free survival. Based on blinded independent central review, radiographic progression-free survival was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after drug discontinuation. Radiographic disease progression was defined by identification of two or more new bone lesions on a bone scan with confirmation (Prostate Cancer Working Group 2 criteria) and/or progression in soft-tissue disease. Time to new antineoplastic therapy was an additional endpoint.
Median radiographic progression-free survival was not reached (NR) in the enzalutamide arm and was 19.4 months (95% confidence interval [CI] = 16.6–NR) in the placebo arm (hazard ratio [HR] = 0.39, 95% CI = 0.30–0.50, P < .0001). A statistically significant improvement was also reported on the enzalutamide arm compared to placebo in time to initiation of a new antineoplastic therapy (HR = 0.28, 95% CI = 0.20–0.40, P < .0001). Overall survival data were not mature at the time of radiographic progression-free survival analysis.
The most common adverse reactions (≥ 5%) that occurred more frequently (≥ 2% over placebo) in patients treated with enzalutamide were hot flush, asthenia/fatigue, hypertension, fractures, and musculoskeletal pain.
The recommended dose is 160 mg (four 40-mg capsules) administered orally once daily with or without food.