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Clinical Research

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

Prostate Cancer and Prostatic Diseases volume 18, pages 122–127 (2015)Cite this article

Subjects

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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Acknowledgements

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.

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Authors and Affiliations

  1. University of Washington, Seattle, WA, USA,

    H H Cheng, R B Montgomery & E Y Yu

  2. Fred Hutchinson Cancer Research Center, Seattle, WA, USA,

    H H Cheng, R Gulati, R B Montgomery & E Y Yu

  3. British Columbia Cancer Agency, Vancouver, BC, Canada,

    A Azad & K N Chi

  4. Sidney Kimmel Cancer Center/Johns Hopkins University, Baltimore, MA, USA,

    R Nadal, H-t Rehman & E S Antonarakis

  5. City of Hope Cancer Center, Duarte, CA, USA

    P Twardowski & S K Pal

  6. Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA,

    U N Vaishampayan & E I Heath

  7. Huntsman Cancer Institute/University of Utah, Salt Lake City, UT, USA,

    N Agarwal & J A Batten

  8. Tisch Cancer Institute/Icahn School of Medicine at Mount Sinai, New York, NY, USA,

    A Leiter & M D Galsky

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  1. H H Cheng
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Corresponding author

Correspondence to E Y Yu.

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Competing interests

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.

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Cheng, H., Gulati, R., Azad, A. et al. Activity of enzalutamide in men with metastatic castration-resistant prostate cancer is affected by prior treatment with abiraterone and/or docetaxel. Prostate Cancer Prostatic Dis 18, 122–127 (2015). https://doi.org/10.1038/pcan.2014.53

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