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

J Urol. 2018 Jan;199(1):147-154. doi: 10.1016/j.juro.2017.08.080. Epub 2017 Aug 19.


Purpose: Enzalutamide significantly prolonged median progression-free survival vs bicalutamide in chemotherapy naïve men with metastatic castration resistant prostate cancer in the TERRAIN (Enzalutamide versus Bicalutamide in Castrate Men with Metastatic Prostate Cancer) trial. In this post hoc analysis we investigated the influence of age on the efficacy and safety of enzalutamide vs bicalutamide in this population.

Materials and methods: Patients were randomized 1:1 to enzalutamide 160 mg per day or bicalutamide 50 mg per day. Progression-free survival, time to prostate specific antigen progression and safety were analyzed post hoc in younger (age less than 75 years) and older (age 75 years or greater) subgroups.

Results: Enzalutamide significantly reduced the risk of disease progression or death vs bicalutamide in patients younger than 75 years (HR 0.38, 95% CI 0.27-0.52, p <0.0001) and 75 years old or older (HR 0.59, 95% CI 0.37-0.92, p = 0.018). Time to prostate specific antigen progression was also significantly prolonged with enzalutamide vs bicalutamide in each subgroup. The adverse event distribution between treatments was similar in each subgroup except for more (5% or greater difference between subgroups) atrial fibrillation, urinary tract infections, falls and decreased appetite as well as less extremity pain and hot flushing in enzalutamide treated patients 75 years old or older, and less back pain and hot flushing in bicalutamide treated patients 75 years old or older. Grade 3 or greater cardiac events were more frequent in enzalutamide treated and bicalutamide treated patients who were 75 years old or older vs younger than 75 years. Fatigue was more frequent in enzalutamide treated patients with a similar distribution in each age subgroup.

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

Keywords: MDV 3100; castration; drug-related side effects and adverse reactions; neoplasm metastasis; prostatic neoplasms.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Age Factors
  • Aged
  • Anilides / adverse effects
  • Anilides / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Double-Blind Method
  • Humans
  • Male
  • Middle Aged
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / therapeutic use
  • Progression-Free Survival
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Tosyl Compounds / adverse effects
  • Tosyl Compounds / therapeutic use*
  • Treatment Outcome


  • Anilides
  • Antineoplastic Agents
  • Benzamides
  • Nitriles
  • Tosyl Compounds
  • Phenylthiohydantoin
  • enzalutamide
  • bicalutamide
  • Prostate-Specific Antigen