Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 122-127 |
| Number of pages | 6 |
| Journal | Prostate Cancer and Prostatic Diseases |
| Volume | 18 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jun 14 2015 |
| Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by the National Cancer Institute at the National Institutes of Health [P50 CA097186 (HHC, RG, EYY), P30 CA006973 (ESA and RN) and T32 CA009515 (HHC)]. We gratefully acknowledge: Maggie So and Kelly Sales for assistance with IRB approvals; Anne Reese, Myan Nguyen, and our clinical colleagues for assistance in identifying patients for this study.
Funding Information:
The coauthors declare the following conflicts of interest: AA declares research support from Astellas (Australia) and an honorarium from Janssen (Canada). RBM declares research support from Medivation/Astellas. UNV declares research support and honoraria from Medivation/Astellas. SKP declares honoraria from Medivation/ Astellas and is a consultant/advisor for Dendreon. MDG declares research support from Janssen, Dendreon, BioMotiv, is a consultant/advisor to Astellas, Dendreon, BioMotiv and has equity in Dual Therapeutics. ESA is a consultant/advisor to Medivation/Astellas, Janssen Biotech and Sanofi US. KNC is a consultant/advisor to Medivation/Astellas and Janssen Biotech. EYY declares research funding from Bristol-Myers Squibb, Dendreon, GTx, Imclone/Lilly, Janssen and OncoGeneX and honoraria from Bayer, Dendreon, Janssen Biotech, Medivation/Astellas and Sanofi US. All remaining authors have declared no conflicts of interest.
Publisher Copyright:
© 2015 Macmillan Publishers Limited All rights.
