Aims: The phase 2 TERRAIN trial compared the efficacy and safety of enzalutamide versus bicalutamide in patients with metastatic castration-resistant prostate cancer who had progressed on luteinising hormone-releasing hormone agonist/antagonist therapy or after bilateral orchiectomy while maintaining castration therapy during the study. An age-effect analysis was pre-specified to investigate the efficacy and safety of enzalutamide versus bicalutamide. Results are presented in younger (<75 years) and older (≥75 years) patients in the TERRAIN population.
Methods: In this double-blind study in North America and Europe, patients were randomised 1:1 to enzalutamide 160 mg/day or bicalutamide 50 mg/day. The primary efficacy end point was centrally assessed progression-free survival (PFS) and a secondary efficacy end point was time to prostate-specific antigen (PSA) progression.
Results: 184 patients were randomised to enzalutamide and 191 patients to bicalutamide. 126 (68.5%) and 119 (62.3%) patients were <75, and 58 (31.5%) and 72 (37.7%) patients were ≥75, in the enzalutamide and bicalutamide arms, respectively. PFS was significantly improved with enzalutamide versus bicalutamide in patients <75 years (median 16.6 vs 5.8 months; hazard ratio [HR] 0.38 [95% confidence interval (CI) 0.27, 0.52]) and patients ≥75 years (median 13.8 vs 6.4 months; HR 0.59 [95% CI 0.37, 0.92]). Median time to PSA progression was similarly significantly improved with enzalutamide versus bicalutamide in younger (median 22.1 vs 8.2 months; HR 0.27 [95% CI 0.18, 0.40]) and older patients (median 16.6 vs 5.8 months; HR 0.33 [95% CI 0.19, 0.57]). Adverse events with enzalutamide were more frequent in older patients (98.3%) versus younger patients (92.8%), but a similar distribution of treatment-related adverse events between treatment arms was observed in either age group.
Conclusions: Enzalutamide had greater efficacy than bicalutamide regardless of age, with superior PFS and time to PSA progression. Enzalutamide showed safety consistent with its known safety profile in both age subgroups.