Enzalutamide is a second-generation androgen receptor (AR) inhibitor that binds to and blocks the AR with higher affinity than previously available AR inhibitors. High activity has been proven in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and in chemotherapy-naive patients with mCRPC. However, its activity in patients previously treated with other novel agents (for example, abiraterone and/or cabazitaxel), remains controversial.
The aim of this retrospective analysis of the Swiss Enzalutamide Named Patient Program was to evaluate clinical efficacy and safety of enzalutamide treatment in patients with mCRPC progressing after docetaxel and other lines of therapy considering different treatment sequences. We report on 44 patients treated with enzalutamide.
The median survival time from diagnosis of CPRC was 41.1 months (95% confidence interval [CI], 32.3-49.8 months). Enzalutamide was used as a second, third, fourth, fifth, sixth, or seventh-line therapy in 13%, 20%, 31%, 20%, 11%, and 2% of patients. The median duration of enzalutamide treatment was 3.0 months (range, 1-21 months). Median progression-free survival was 3.0 months (95% CI, 2.4-3.7 months). The estimated median overall survival was 6.3 months (95% CI, 4.6-8.1 months). Sixteen patients (36.4%) had a prostate-specific antigen decrease of ≥ 30%, and 11 patients (25.0%) of ≥ 50%, respectively. In multivariate analysis, the absence of previous therapy with abiraterone and a prostate-specific antigen response of ≥ 50% on enzalutamide therapy were significantly associated with overall survival on enzalutamide treatment.
Our results show that enzalutamide has modest activity in extensively pretreated patients. However, there is a subgroup of patients achieving benefit from enzalutamide therapy even after pretreatment with abiraterone.