Efficacy and Safety of Enzalutamide vs Bicalutamide in Younger and Older Patients with Metastatic Castration-resistant Prostate Cancer in the TERRAIN Trial

Enzalutamide significantly prolonged median progression-free survival vs bicalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer in TERRAIN. A post hoc analysis investigated the influence of age on efficacy and safety of enzalutamide vs bicalutamide in this population.

Patients were randomized 1:1 to enzalutamide 160 mg/day or bicalutamide 50 mg/day. Progression-free survival, time to prostate-specific antigen progression and safety were analyzed post hoc in younger (<75 years) and older (≥75 years) subgroups.

Enzalutamide significantly reduced the risk of disease progression or death vs bicalutamide in patients age <75 (hazard ratio 0.38; 95% confidence interval 0.27-0.52; p <0.0001) and ≥75 (hazard ratio 0.59; 95% confidence interval 0.37-0.92; p = 0.018). Time to prostate-specific antigen progression was also significantly prolonged with enzalutamide vs bicalutamide in both subgroups. Adverse event distribution between treatments was similar in each subgroup, except for (≥5% difference between subgroups) more atrial fibrillation, urinary tract infections, falls and decreased appetite in enzalutamide-treated patients age ≥75; less pain in extremity and hot flush in enzalutamide-treated patients age ≥75; and less back pain and hot flush in bicalutamide-treated patients age ≥75. Grade ≥3 cardiac events were more frequent in both enzalutamide-treated and bicalutamide-treated patients age ≥75 vs <75. Fatigue was more frequent in enzalutamide-treated patients, with similar distributions in both age subgroups.

Enzalutamide improved clinical outcomes vs bicalutamide irrespective of age. Increased falls and cardiac events suggest caution when prescribing to older patients (≥75 years) with significant comorbidity.

The Journal of urology. 2017 Aug 18 [Epub ahead of print]

D Robert Siemens, Laurence Klotz, Axel Heidenreich, Simon Chowdhury, Arnauld Villers, Benoit Baron, Steve van Os, Nahla Hasabou, Fong Wang, Ping Lin, Neal D Shore

Centre for Applied Urological Research, Queen's University, Kingston, Ontario, Canada. Electronic address: ., Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Department of Urology, University of Cologne, Cologne, Germany., Guy's, King's and St Thomas' Hospitals, London, UK., Department of Urology, Lille University, Lille, France., Astellas Pharma, Inc., Leiden, the Netherlands., Astellas Pharma, Inc., Northbrook, IL, USA., Medivation, Inc., which was acquired by Pfizer, Inc. in September 2016, San Francisco, CA, USA., Carolina Urologic Research Center, Myrtle Beach, SC, USA.