Fatigue is common in men with advanced prostate cancer and may be related to disease progression, ongoing systemic therapy, comorbidities, concomitant medications or a combination of these factors. Fatigue adverse events (AEs) across four double-blind, randomised, placebo- or bicalutamide-controlled trials of enzalutamide (ENZA) for men with metastatic castration-resistant prostate cancer are summarised to assess incidence, timing and effect of age on fatigue.
Safety data from ENZA trials (AFFIRM NCT00974311, PREVAIL NCT01212991, TERRAIN NCT01288911 and STRIVE NCT01664923) with men with metastatic castration-resistant prostate cancer were evaluated for fatigue AEs. As per CTCAE, v 4.0, fatigue is defined as a state of generalised weakness, with a pronounced inability to summon sufficient energy to accomplish daily activities. Analyses included unadjusted and per-100 patient-years fatigue AE incidences assessed by grade, time and age (
With 2051 men in the ENZA arms and 1630 in the control arms, total treatment exposure patient-years were longer for ENZA (range, 219–1294) vs control (range, 143–560). The unadjusted percentages of men reporting fatigue for all grades were slightly higher in the ENZA arms (range, 28% − 38%) vs the control arms (range, 20% − 29%). Grade 3 fatigue AEs were reported by
Early-onset fatigue occurred slightly more frequently in ENZA-treated patients. Irrespective of treatment, fatigue was more common in men ≥75 years and was grade 3 in a small percentage of men.
Clinical trial identification
Legal entity responsible for the study
Astellas Pharma, Inc. and Medivation, Inc.
Astellas Pharma, Inc. and Medivation Inc.
S. Chowdhury: Advisory board member: Sanofi, Astellas, Novartis, Janssen, Bayer, Essa, Pfizer, Clovis. Corporate-sponsored research: Sanofi, Astellas.
N. Shore: Advisory board member: Astellas, Bayer, Dendreon, Ferring, Janssen, Sanofi, Takeda.
F. Saad: Advisory board member and corporate-sponsored research: Astellas, Janssen, Sanofi, Bayer.
C.S. Higano: Dendreon, Bayer, Medivation, Ferring, Abbvie, Pfizer, BHR, Orion Corp, Emergent. BioSolutions, MorphoSys, Churchill, Astellas, Clovis, Cato Research, PAREXEL, Blue Earth, Valeant, Algeta, Aragon, AstraZeneca, Genentech, Millenium, Sanofi, Teva, Exelixis.
K. Fizazi: Advisory board member: Amgen, Janssen, Sanofi, Orion, Astellas, Genentech, Bayer, Essa.
P. Iversen: Ad boards and lecturing: Astellas, Medivation, Janssen, Sanofi, Amgen. Investigator in industry sponsored trials: Astellas, Medivation, Janssen, Bavarian Nordic.
A. Heidenreich: Advisory board member: Astellas, Bayer, Dendreon, Jansen, Sanofi. Corporate-sponsored research: Astellas, Bayer.
T. Ueda: Corporate-sponsored research: Astellas.
D. Phung: Employee of Astellas.
A. Krivoshik: Employee of Astellas. Owns Abbott and Abbvie stock.
F. Wang, K. Wu: Employee of Medivation. Owns Medivation stock.
B. Tombal: Advisory board member and corporate-sponsored research: Amgen, Jansen, Ipsen, Sanofi, and Takeda (for whom he is also a board member).
All other authors have declared no conflicts of interest.