On December 16, 2019, the FDA approved a new indication for enzalutamide (Xtandi; Astellas Pharma) for the treatment of patients with metastatic castration-sensitive prostate cancer (CSPC). Enzalutamide was previously approved for patients with castration-resistant prostate cancer.
The approval was based on efficacy results from the ARCHES clinical trial of 1150 patients with metastatic CSPC who were randomized (1:1) to oral enzalutamide 160 mg once daily (N = 574) or to oral placebo once daily (N = 576). All patients received a gonadotropin-releasing hormone analog or had previous bilateral orchiectomy.
The main efficacy measure was radiographic progression-free survival (PFS), which 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 the identification of ≥2 new bone lesions on a bone scan with confirmation and/or progression in soft-tissue disease. The time to new antineoplastic therapy was an additional end point.
The median radiographic PFS was not reached in the enzalutamide arm versus 19.4 months (95% confidence interval, 16.6-not reached) in the placebo arm (P <.0001). A significant improvement was also seen with enzalutamide versus placebo in the time to initiation of a new antineoplastic therapy (P <.0001). The overall survival data were not mature at the time of the analysis.
The most common (≥5%) adverse reactions occurring more frequently (≥2% vs placebo) with enzalutamide in this study were hot flush, asthenia/fatigue, hypertension, fractures, and musculoskeletal pain.