Poster Presentation Joint 2016 COSA and ANZBCTG Annual Scientific Meeting

Efficacy and safety of enzalutamide versus bicalutamide in younger and older patients with metastatic castration-resistant prostate cancer in the TERRAIN trial (#214)

D Robert Siemens 1 , Laurence Klotz 2 , Axel Heidenreich 3 , Simon Chowdhury 4 , Arnauld Villers 5 , Benoit Baron 6 , Steve Van Os 6 , Nahla Hasabou 7 , Scott Brown 8 , Fong Wang 9 , David Forer 9 , Neal D Shore 10
  1. Centre for Applied Urological Research, Ontario, Canada
  2. Sunnybrook Health Sciences Centre, Toronto, Canada
  3. Department of Urology, University of Cologne, Cologne, Germany
  4. Guy’s, King’s and St Thomas’ Hospitals, London, UK
  5. Department of Urology, Lille University, Lille, France
  6. Astellas Pharma, Inc,, Leiden, The Netherlands
  7. Astellas Pharma, Northbrook, USA
  8. Astellas Pharma , North Ryde, New South Wales, Australia
  9. Medivation, Inc, San Francisco, USA
  10. Carolina Urologic Research Center, Myrtle Beach, USA

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.