Activity of enzalutamide in men with metastatic castration-resistant prostate cancer is affected by prior treatment with abiraterone and/or docetaxel

Background:enzalutamide and abiraterone are new androgen-axis disrupting treatments for metastatic castration-resistant prostate cancer (mcrpc). we examined the response and outcomes of enzalutamide-treated mcrpc patients in the real-world context of prior treatments of abiraterone and/or docetaxel.methods:we conducted a seven-institution retrospective study of mcrpc patients treated with enzalutamide between january 2009 and february 2014. we compared the baseline characteristics, psa declines, psa progression-free survival (psa-pfs), duration on enzalutamide and overall survival (os) across subgroups defined by prior abiraterone and/or docetaxel.results:of 310 patients who received enzalutamide, 36 (12%) received neither prior abiraterone nor prior docetaxel, 79 (25%) received prior abiraterone, 30 (10%) received prior docetaxel and 165 (53%) received both prior abiraterone and prior docetaxel. within these groups, respectively, ⩾30% psa decline was achieved among 67, 28, 43 and 24% of patients; psa-pfs was 5.5 (95% ci 4.2–9.1), 4.0 (3.2–4.8), 4.1 (2.9–5.4) and 2.8 (2.5–3.2) months; median duration of enzalutamide was 9.1 (7.3–not reached), 4.7 (3.7–7.7), 5.4 (3.8–8.4) and 3.9 (3.0–4.6) months. median os was reached only for the patients who received both prior abiraterone and docetaxel and was 12.2 months (95% ci 10.7–16.5). 12-month os was 78% (59–100%), 64% (45–90%), 77% (61–97%) and 51% (41–62%). of 70 patients who failed to achieve any psa decline on prior abiraterone, 19 (27%) achieved ⩾30% psa decline with subsequent enzalutamide.conclusions:the activity of enzalutamide is blunted after abiraterone, after docetaxel, and still more after both, suggesting subsets of overlapping and distinct mechanisms of resistance.