Is there an antiandrogen withdrawal syndrome with enzalutamide?

Abstract

Objective: To examine prostate-specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide.

Methods: We retrospectively identified 30 consecutive patients with metastatic prostate cancer who were treated with enzalutamide after docetaxel. Post-discontinuation PSA results were available for all patients and were determined at 2-weekly intervals until starting further anticancer systemic therapy. PSA withdrawal response was defined as a PSA decline by ≥50% from the last on-treatment PSA, with a confirmed decrease ≥3 weeks later. Patient characteristics were evaluated in relation to the AAWS using univariate logistic regression analysis.

Results: The median (range) patient age was 70.5 (56-86) years and the median (range) follow-up was 9.0 (0.5-16) months. The most common metastatic sites were the bone (86.7%) and lymph nodes (66.7%). Most patients (70%) had previously received abiraterone and 12 patients (40%) had also received cabazitaxel. The median (range) treatment duration with enzalutamide was 3.68 (1.12-21.39) months. PSA levels after enzalutamide withdrawal were monitored for a median (range) time of 35 (10-120) days. Only one patient (3.3%) had a confirmed PSA response ≥50% after enzalutamide discontinuation. One patient (3.3%) had a confirmed PSA response of between 30 and 50% and another patient (3.3%) had an unconfirmed PSA response of between 30 and 50%. The median overall survival was 15.5 months (95% CI 8.1-24.7). None of the factors analysed in the univariate analysis were significant predictors of PSA decline after enzalutamide discontinuation.

Conclusions: This retrospective study provides the first evidence that enzalutamide may have an AAWS in a minority of patients with metastatic castration-resistant prostate cancer. Further studies are needed to confirm the existence of an enzalutamide AAWS and to assess its relevance in prostate cancer management.

Keywords: androgen receptor gene F876L mutation; androgen receptor targeting; antiandrogen withdrawal syndrome; castration-resistant prostate cancer; enzalutamide; hormone therapy.