The effect of prior abiraterone (Abi) use on the activity of enzalutamide (Enza) in men with mCRPC.

Abstract

18 Background: Enzalutamide (Enza) and abiraterone (Abi) are next generation hormonal agents for metastatic castration resistant prostate cancer (mCRPC). Whether these agents can be effectively sequenced is not yet well understood. Results of retrospective analyses of Abi after prior Enza have demonstrated modest responses of brief duration, suggesting common resistance pathways. Here, we retrospectively analyze response to Enza with or without prior Abi treatment. Methods: We retrospectively reviewed 195 patients from seven academic centers treated with Enza between January 2009 and August 2013. Data were collected on disease characteristics, prior therapies, and prostate-specific antigen (PSA) values at baseline and while on treatment. Logistic regression was used to evaluate association between 30% or greater PSA decline on Enza and either prior Abi treatment or 30% or greater PSA decline on prior Abi after accounting for potential confounders. Results: One hudred eighty three patients had non-missing PSA starting and nadir values on Enza, with starting PSA median 102.0 (range 1.1–5007.0) ng/mL. Overall, 42% (76 of 183) of Enza-treated patients achieved a 30% or greater PSA decline, with 39% (58 of 150) response among prior Abi-treated patients and 55% (18 of 33) response among Abi-naïve patients. Of 79 patients who lacked significant response to prior Abi, 30% (25 of 79) achieved a 30% or greater PSA decline and 19% (15 of 79) achieved a 50% or greater PSA decline with subsequent Enza. Odds of achieving a 30% or greater PSA response on Enza was 2.3 times higher for Abi-naïve patients versus prior Abi-treated patients (95% CI 1.0–5.5, P=0.06) and 1.9 times higher for Abi-responders vs Abi-non-responders (95% CI 1.0–3.7, P=0.06) after adjusting for prior docetaxel and concurrent steroid use. Conclusions: In this multi-center retrospective study, 39% of patients achieved a 30% or greater PSA decline with Enza after prior Abi treatment. While the activity of Enza appears to be blunted in the post-Abi setting, PSA declines still occur in a meaningful proportion of patients. Notably, 30% of patients without significant response to prior Abi responded to subsequent treatment with Enza, suggesting a subset of men with distinct biological resistance pathways. Data will be updated at the time of presentation.