Impact of prior therapy with ketoconazol or abiraterone and pattern of PSA response in a cohort of patients with metastatic castrate resistant prostate cancer (mCRPC) receiving enzalutamide for postdocetaxel

Background: Enzalutamide has proved activity in second line setting after progression to docetaxel-based chemotherapy in patients with mCRPC in a phase III trial compared to placebo. Objective: To analyze PSA progression free survival, patterns of PSA response, the impact of prior ketoconazol or abiraterone therapy and its relationship with survival in 40 patients treated within an expanded access program in two University Hospitals in Spain. Methods: All patients received Enzalutamide 160 mg per day until clinical progression. All patients had castrate levels of Testosterone and had failed to docetaxel. PSA levels were performed basally and followed under therapy every 4 weeks. Definitions of PSA response and progression were according to PCWG2 criteria. Four patients had previously been treated with Abiraterone, 7 patients with Ketoconazol and 1 patient both. Median number of cycles of docetaxel was 8 (2-12). 5 patients had been treated with Cabazitaxel. Results: Median age was 72 (46-88). Median ECOG 1 (0-2). Median basal PSA levels were 67.5 (2.7-886) U/L. PSA response after 4 weeks of therapy: 9/40 patients (22%) did not response, 19/40 47.5%, showed a reduction >30% and 11/40, 27.5% >50%. All patients achieved maximum PSA response by week 8. No flare effect was observed. Median time to PSA progression was 5.25 months (0.47-12.5); 6/40, 15% of patients maintained PSA response for more than a year. Median survival was 8.83 months (0.63-12.53). Median survival for patients with a PSA response >30% at week 4 was 11.23 (4.27-14.8) vs. 7.3 (0.63-12.63) for other patients. No differences in PSA response were observed for patients previously treated with ketoconazol. Of the five patients previously treated with abiraterone, 2 had PSA response, one of them for less than 4 weeks Conclusions: No PSA flare effect was observed under Enzalutamide. PSA response to Enzalutamide was observed by week 4 in 90% of patients that responded. PSA response >30% at week 4 might be a predictor of survival. Prior ketoconazol did not affect PSA response to Enzalutamide.