Sequential Treatment with Abiraterone and Enzalutamide in Swedish Patients with Metastatic Castration-Resistant Prostate Cancer

1. Abstract 1.1. Background: Sequential treatment with abiraterone followed by enzalutamide or vice versa in patients with metastatic castration-resistant prostate cancer (mCRPC) is not generally recommended in Sweden. However, selected patients, with few treatment options, have received both treatments with promising results. 1.2. Objective: To determine whether patients with mCRPC could benefit from receiving abiraterone or enzalutamide as second-line therapy and if the sequencing order has any significance. 1.3. Design, setting, and participants: This retrospective register study enrolled 66 patients with mCRPC treated with abiraterone followed by enzalutamide or vice versa at Uppsala University Hospital between the years of 2012 and 2019. The median follow-up was 28.8 months. 1.4. Outcome measurements and statistical analysis: Prostate-specific antigen (PSA) response rates, progression-free survival (PFS) of the firstand second-line treatment, combined PFS and overall survival were compared between the two study groups and between responders and non-responders to both treatments using log-rank analysis and multivariate Cox regression. 1.5. Results and limitations: Thirty patients (47%) responded with a PSA decline to both treatments, resulting in a significantly longer combined PFS compared to non-responders (Responders, 19.0 months vs. Non-responders, 12.9 months; P = 0.039). The PSA response rate to second-line treatment with enzalutamide was 68% and to second-line treatment with abiraterone 33% (P = 0.023). No significant differences were found in overall survival between non-responders and responders. Limitations include the retrospective design, the few numbers of patients and the short follow-up. 1.6. Conclusions: A substantial PSA response was obtained by adding a second-line anti-androgen to patients with mCRPC. Treating with abiraterone followed by enzalutamide was more effective than the reverse order.