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

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)).

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.

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.

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.

Prostate cancer and prostatic diseases. 2021 Sep 13 [Epub ahead of print]

Bertrand F Tombal, Stephen J Freedland, Andrew J Armstrong, Tomasz M Beer, Arnulf Stenzl, Cora N Sternberg, Maha Hussain, Arijit Ganguli, Krishnan Ramaswamy, Hemant Bhadauria, Cristina Ivanescu, James Turnbull, Stefan Holmstrom, Fred Saad

Urology, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium., Urology, Center for Integrated Research in Cancer and Lifestyle, Cedars-Sinai Medical Center, Los Angeles, CA, USA., School of Medicine, Duke Cancer Institute Center for Prostate & Urologic Cancers, Durham, NC, USA., Hematology/Medical Oncology, OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Urology, University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany., Englander Institute for Precision Medicine, Medical Oncology, Weill Cornell Medicine, Meyer Cancer Center, New York, NY, USA., Medicine, Lurie Cancer Center, Northwestern University, Chicago, IL, USA., HEOR, Astellas Pharma Inc, Northbrook, IL, USA., HEOR, Pfizer Inc, New York, NY, USA., Medical Affairs, Astellas Pharma Inc., Northbrook, IL, USA., Statistics, IQVIA, Amsterdam-Zuidoost, the Netherlands., Patient Centered Endpoints, IQVIA, New York, NY, USA., HEOR, Astellas Pharma Inc., Leiden, the Netherlands., Urology, University of Montréal Hospital Center, Montréal, QC, Canada. .