ASCO GU 2018: Retrospective Analysis of Fatigue in Men with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide

San Francisco, CA ( Enzalutamide, an androgen axis inhibitor, has had an increasingly important role in the management of advanced prostate cancer. Currently approved for metastatic castration-resistant prostate cancer (mCRPC), there is growing evidence it may have a role in earlier stages of prostate cancer progression. Indeed, at this very conference, reports of PROSPER, a clinical trial of enzalutamide in the setting of cM0 CRPC, is being reported – preliminary data suggests significant PFS benefit!

However, a common adverse effect of Enza in clinical practice has been fatigue. Unfortunately, the fatigue while taking Enzalutamide is poorly understood and may limit the use of this life-prolonging drug. In this abstract, the authors try to elucidate the factors associated with fatigue on Enza by retrospectively assessing all men treated with Enza for mCRPC at Princess Margaret Cancer Centre (Toronto, ON) from August 2010 and July 2016.

During that time frame, 415 men were started on Enza for mCRPC; median age at diagnosis was 66 years (range 42-94) and median time to castration-resistance (TTCR) was 113 days (4 months). Men had been pretreated with docetaxel (21%) and abiraterone (26%) in about a quarter of the cases. As for the sites of metastases, bone was the most common site of metastasis (76%) followed by lymph nodes (45%) and visceral (20%). Concurrent corticosteroid use was 18%, primarily in patients previously treated with abiraterone.

PSA response, defined as ≥50% reduction, was 55%. Median duration on Enza was 224 days (7-8 months).

Fatigue on Enza occurred in 178 patients (43%), with 56 (13%) of men required a dose-reduction due to fatigue specifically. 26 men (6%) eventually discontinued Enza due to fatigue.

On multivariable analysis, comparing clinicopathologic factors and disease characteristics, duration of exposure to androgen deprivation, markers of systemic inflammation (such as increased NLR and platelets) and advanced age appear to be associated with Enza-related fatigue and discontinuation. Of note, variables included in the analysis were based on significant findings from univariate analysis.

Importantly, the use of corticosteroids was not associated with development of fatigue. Corticosteroids were trialed in 6 patients with fatigue and only 2 had mild improvement.

Speaker: Srikala Sridhar, MD, FRCPC

Co-Authors: Alan D. Smith, Nazanin Fallah-Rad, Aaron Richard Hansen

Institution(s): Princess Margaret Hospital, Toronto, ON, Canada

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA