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. 2015 Jun;18(2):122-7.
doi: 10.1038/pcan.2014.53. Epub 2015 Jan 20.

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

H H Cheng  1 , R Gulati  2 , A Azad  3 , R Nadal  4 , P Twardowski  5 , U N Vaishampayan  6 , N Agarwal  7 , E I Heath  6 , S K Pal  5 , H-T Rehman  4 , A Leiter  8 , J A Batten  7 , R B Montgomery  1 , M D Galsky  8 , E S Antonarakis  4 , K N Chi  3 , E Y Yu  1
Affiliations

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

H H Cheng et al. Prostate Cancer Prostatic Dis. 2015 Jun.

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.

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Conflict of interest statement

CONFLICT OF INTEREST:

The coauthors declare the following conflicts of interest: AAA 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.

Figures

Figure 1
Figure 1
PSA waterfall plots showing the maximal percent PSA change from baseline in patients who received (a) enzalutamide (Abi+Doce-Naive); (b) enzalutamide after prior abiraterone (Prior-Abi); (c) enzalutamide after prior docetaxel (Prior-Doce); (d) enzalutamide after prior abiraterone and docetaxel (Prior-Abi+Doce).
Figure 2
Figure 2
Kaplan-Meier survival curves of (a) PSA-progression-free survival (P = 0.0004) and (b) overall survival (P = 0.008) for patients who received enzalutamide (Abi+Doce-Naive), enzalutamide after prior abiraterone (Prior-Abi), enzalutamide after prior docetaxel (Prior-Doce), and enzalutamide after prior abiraterone and docetaxel (Prior-Abi+Doce).
See this image and copyright information in PMC

Comment in

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