Is there an anti-androgen withdrawal effect with enzalutamide?

Abstract

200 Background: The second generation anti-androgen enzalutamide has demonstrated improved survival in patients with metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. While an anti-androgen withdrawal effect has been reported for bicalutamide, flutamide, and other non-steroidal and steroidal anti-androgens, there is no published evidence of any withdrawal effect with enzalutamide. Methods: We retrospectively identified 30 consecutive patients with advanced prostate cancer who were treated with enzalutamide post-docetaxel at three London hospitals. All patients were withdrawn from enzalutamide due to clinical (73%), PSA (87%) and/or radiological progression (47%). Post-discontinuation prostate-specific antigen (PSA) results were available for all patients and were determined two-weekly for at least six weeks until starting further anti-cancer treatment. PSA withdrawal response was defined as a 50% decline in PSA from baseline, with a confirmed decrease after 3 weeks or more. Clinical tumor and patient characteristics were evaluated in relation to the withdrawal effects using multivariate logistic regression analyses. Results: Median age was 71 (range 54 to 87). The median follow-up was 5.4 months (range: 0.5 to 16.0 months). At enzalutamide initiation, ECOG performance status was 0 and 1 in 10% and 69% of patients, respectively. The most common metastatic sites were bone (87%), lymph nodes (68%), liver (17%), and lung (6%). Most patients (70%) had been on abiraterone previously and 11 patients (37%) had also received prior cabazitaxel. The median treatment duration with enzalutamide was 3.7 months. Only one patient (3%) had a confirmed PSA response of 50% or more after enzalutamide discontinuation and two patients (7%) had a confirmed PSA response between 30% and 50%. None of the clinical variables assessed in relation to withdrawal effects were found to be statistically significantly associated. Conclusions: This preliminary case series represents the first clinical evidence that enzalutamide may have an anti-androgen withdrawal effect in a minority of patients. These results warrant further prospective and controlled validation of a potential enzalutamide withdrawal effect and its clinical relevance in prostate cancer management.