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Clinical activity of enzalutamide in Docetaxel‐naïve and Docetaxel‐pretreated patients with metastatic castration‐resistant prostate cancer
Author(s) -
Nadal Rosa,
Zhang Zhe,
Rahman Hibba,
Schweizer Michael T.,
Denmeade Samuel R.,
Paller Channing J.,
Carducci Michael A.,
Eisenberger Mario A.,
Antonarakis Emmanuel S.
Publication year - 2014
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22874
Subject(s) - enzalutamide , medicine , docetaxel , prostate cancer , urology , oncology , placebo , gastroenterology , androgen receptor , cancer , pathology , alternative medicine
Abstract BACKGROUND Two randomized clinical trials have demonstrated a survival advantage with enzalutamide over placebo in both docetaxel (D)‐pretreated and D‐naïve metastatic castration‐resistant prostate cancer (mCRPC) patients. Cross‐resistance between androgen receptor‐directed therapies and taxanes has been suggested, possibly leading to lower efficacy of enzalutamide in the post‐D setting. METHODS We aimed to examine the impact of prior D treatment on the clinical activity of enzalutamide in patients with mCRPC. We retrospectively reviewed an institutional database to identify men with mCRPC treated with standard‐of‐care enzalutamide. Patients were classified as D‐naïve or D‐pretreated. The efficacy end points were prostate‐specific antigen (PSA) response rates (≥ 50% PSA decline), time to PSA progression (TTPP) and clinical/radiographic progression‐free survival (PFS) in response to enzalutamide. Differences between groups (D‐naïve and D‐pretreated) were assessed by univariate and multivariable analyses using logistic and Cox regression models. RESULTS One‐hundred‐seven (107) consecutive patients were included: 60 were D‐pretreated and 47 were D‐naïve. PSA responses were 43.2% in D‐naïve patients and 25.4% in D‐pretreated patients ( P = 0.089). Median TTPP was 7.2 months (95% CI = 4.5 – 17.2) in the D‐naïve group versus 2.6 mo (95% CI = 1.9 – 3.5) in the D‐pretreated group ( P < 0.0001). Median PFS was not reached for D‐naïve men and was 3.3 mo (95% CI = 2.5 – 4.8) for D‐pretreated men ( P < 0.0001). After adjusting for potential confounders including prior abiraterone use, differences remained statistically significant for TTPP (HR = 2.32; 95% CI = 1.19 – 4.50; P = 0.013) and marginally significant for PFS (HR = 1.90; 95% CI = 0.94 – 3.84; P = 0.073) in multivariable analyses. Among patients who achieved a PSA response to enzalutamide (n = 34), results suggested a trend towards shorter duration of response in D‐pretreated patients. CONCLUSIONS The clinical activity of enzalutamide appears to be blunted in patients who have previously received docetaxel chemotherapy. These results support the concept of cross‐resistance between these two agents. Prostate 74:1560–1568, 2014 . © 2014 Wiley Periodicals, Inc.