Impact of enzalutamide on patient-reported fatigue in patients with prostate cancer: data from the pivotal clinical trials.

Journal Article (Journal Article)

BACKGROUND: Fatigue is a multifactorial symptom commonly reported by patients with prostate cancer as a result of disease and treatment. This study assesses the impact enzalutamide has on patient-reported fatigue ("fatigue") by using patient-reported outcomes from four pivotal, placebo-controlled trials of enzalutamide (ARCHES (NCT02677896), PROSPER (NCT02003924), PREVAIL (NCT01212991), and AFFIRM (NCT00974311)). METHODS: Fatigue was assessed in the individual studies using the Functional Assessment of Cancer Therapy-Prostate item GP1 at baseline, weeks 13 or 17, and every 12 weeks until disease progression. Longitudinal changes were assessed using mean scores and mixed-model repeated measures. RESULTS: The fatigue rates at baseline were higher in patients with later-stage disease (metastatic and/or castration-resistant prostate cancer (CRPC)) and among patients who had already received prior treatment lines; rates ranged between 58% in PROSPER (nonmetastatic CRPC) and 86% in AFFIRM (post-docetaxel metastatic CRPC). Irrespective of disease state, initiation of enzalutamide or placebo resulted in an early increase of fatigue (by weeks 13 or 17), with fatigue levels stabilizing thereafter. At last assessment, ≥55% of patients reported fatigue improvement or stabilization in all trials compared to baseline. More patients reported fatigue worsening by ≥1 or ≥2 units with enzalutamide plus androgen deprivation therapy (ADT) than with placebo plus ADT in ARCHES, PROSPER, and PREVAIL, but the between-group difference was <10% in all trials. CONCLUSIONS: The levels of fatigue were greater in mCRPC and lower in earlier states of disease. In all trials, patients reported a small increase in fatigue for the first 13-17 weeks after starting enzalutamide or placebo, with slightly greater fatigue with enzalutamide in all studies except AFFIRM, but fatigue stabilized or improved thereafter. This suggests a role for clinical management of fatigue to help patients cope early in treatment.

Full Text

Duke Authors

Cited Authors

  • Tombal, BF; Freedland, SJ; Armstrong, AJ; Beer, TM; Stenzl, A; Sternberg, CN; Hussain, M; Ganguli, A; Ramaswamy, K; Bhadauria, H; Ivanescu, C; Turnbull, J; Holmstrom, S; Saad, F

Published Date

  • February 2022

Published In

Volume / Issue

  • 25 / 2

Start / End Page

  • 288 - 295

PubMed ID

  • 34518652

Pubmed Central ID

  • PMC9184276

Electronic International Standard Serial Number (EISSN)

  • 1476-5608

Digital Object Identifier (DOI)

  • 10.1038/s41391-021-00447-9


  • eng

Conference Location

  • England