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

Background: Fatigue is a frequent, multifactorial symptom in prostate cancer arising from disease and treatment. This study assessed the impact of enzalutamide on patient-reported fatigue using data from four pivotal, randomized, placebo-controlled trials (ARCHES, PROSPER, PREVAIL, AFFIRM). Methods: Fatigue was measured using FACT-P item GP1 ("I have a lack of energy") at baseline, weeks 13 or 17, and every 12 weeks until progression. Longitudinal changes were analyzed using mean scores and mixed-model repeated measures. Results: Baseline fatigue was more prevalent in later-stage and previously treated patients, ranging from 58% (PROSPER, nmCRPC) to 86% (AFFIRM, post-docetaxel mCRPC). Initiation of enzalutamide or placebo produced an early increase in fatigue (by weeks 13/17) that stabilized thereafter. At last assessment, ≥55% of patients had fatigue improvement or stabilization across trials. More patients experienced worsening by ≥1 or ≥2 units with enzalutamide plus ADT than with placebo in ARCHES, PROSPER, and PREVAIL, but fewer did so in AFFIRM. Conclusions: Patient-reported fatigue varied by disease stage. Across trials, a small early increase in fatigue occurred after starting enzalutamide or placebo, with subsequently greater fatigue during enzalutamide in all studies except AFFIRM, after which fatigue stabilized or improved. Early clinical management of fatigue may help patients cope when initiating therapy.