Incidence and Characterization of Antiandrogen Withdrawal Syndrome After Discontinuation of Treatment With Enzalutamide in Castration-resistant Prostate Cancer

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BackgroundAntiandrogen withdrawal syndrome (AAWS), manifested as a prostate-specific antigen (PSA) decline after discontinuation of a first-generation antiandrogen has been well characterized. The objective of the present study was to assess the incidence of AAWS with enzalutamide in men with metastatic castration-resistant prostate cancer.Patients and MethodsPatients from a single-institution cohort with metastatic castration-resistant prostate cancer who had discontinued enzalutamide after PSA or radiographic progression were included. AAWS after enzalutamide was defined as any PSA decline after discontinuation of enzalutamide. The baseline patient, disease, and treatment characteristics were compared between patients with and without AAWS after enzalutamide. Statistical analysis of the baseline characteristics included descriptive statistics using the Wilcoxon rank sum test and the Fisher exact test. The median duration of enzalutamide therapy was compared using the log-rank test, and the progression-free survival of the patients with AAWS was evaluated using the Kaplan-Meier method.ResultsOf 47 eligible patients, 5 experienced AAWS after enzalutamide discontinuation. The PSA response in these 5 patients was 84%, 32%, 17%, 15%, and 15%. The median AAWS response time until subsequent PSA progression was 3.3 months. No patient, disease, or treatment characteristics differed among the patients with and without AAWS after enzalutamide discontinuation.ConclusionTo the best of our knowledge, this is the largest reported cohort documenting the incidence and characterization of AAWS after enzalutamide to date. The AAWS frequency after enzalutamide was low and of short duration. No patient- or disease-related characteristics were associated with AAWS with enzalutamide. The occurrence of AAWS after enzalutamide was not clinically meaningful. Thus, accounting for this phenomenon in clinical practice or trial designs could be unnecessary.Micro-AbstractAntiandrogen withdrawal syndrome (AAWS) is a well-reported phenomenon with first-generation antiandrogens. AAWS is a less well-defined phenomenon with the antiandrogen enzalutamide. The present retrospective evaluation of men with progression during enzalutamide therapy failed to demonstrate a clinically significant incidence of enzalutamide withdrawal. These findings argue against the need to account for AAWS with enzalutamide in clinical trial designs.

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