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

H. H. Cheng, R. Gulati, A. Azad, R. Nadal, P. Twardowski, U. N. Vaishampayan, N. Agarwal, E. I. Heath, S. K. Pal, H. T. Rehman, A. Leiter, J. A. Batten, R. B. Montgomery, M. D. Galsky, Emmanuel Antonarakis, K. N. Chi, E. Y. Yu

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)122-127
Number of pages6
JournalProstate Cancer and Prostatic Diseases
Volume18
Issue number2
DOIs
StatePublished - Jun 14 2015

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docetaxel
Castration
Prostatic Neoplasms
Therapeutics
Disease-Free Survival
Survival
MDV 3100
abiraterone

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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Activity of enzalutamide in men with metastatic castration-resistant prostate cancer is affected by prior treatment with abiraterone and/or docetaxel. / Cheng, H. H.; Gulati, R.; Azad, A.; Nadal, R.; Twardowski, P.; Vaishampayan, U. N.; Agarwal, N.; Heath, E. I.; Pal, S. K.; Rehman, H. T.; Leiter, A.; Batten, J. A.; Montgomery, R. B.; Galsky, M. D.; Antonarakis, Emmanuel; Chi, K. N.; Yu, E. Y.

In: Prostate Cancer and Prostatic Diseases, Vol. 18, No. 2, 14.06.2015, p. 122-127.

Research output: Contribution to journalArticle

Cheng, HH, Gulati, R, Azad, A, Nadal, R, Twardowski, P, Vaishampayan, UN, Agarwal, N, Heath, EI, Pal, SK, Rehman, HT, Leiter, A, Batten, JA, Montgomery, RB, Galsky, MD, Antonarakis, E, Chi, KN & Yu, EY 2015, '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, vol. 18, no. 2, pp. 122-127. https://doi.org/10.1038/pcan.2014.53
Cheng, H. H. ; Gulati, R. ; Azad, A. ; Nadal, R. ; Twardowski, P. ; Vaishampayan, U. N. ; Agarwal, N. ; Heath, E. I. ; Pal, S. K. ; Rehman, H. T. ; Leiter, A. ; Batten, J. A. ; Montgomery, R. B. ; Galsky, M. D. ; Antonarakis, Emmanuel ; Chi, K. N. ; Yu, E. Y. / Activity of enzalutamide in men with metastatic castration-resistant prostate cancer is affected by prior treatment with abiraterone and/or docetaxel. In: Prostate Cancer and Prostatic Diseases. 2015 ; Vol. 18, No. 2. pp. 122-127.
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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.",
author = "Cheng, {H. H.} and R. Gulati and A. Azad and R. Nadal and P. Twardowski and Vaishampayan, {U. N.} and N. Agarwal and Heath, {E. I.} and Pal, {S. K.} and Rehman, {H. T.} and A. Leiter and Batten, {J. A.} and Montgomery, {R. B.} and Galsky, {M. D.} and Emmanuel Antonarakis and Chi, {K. N.} and Yu, {E. Y.}",
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TY - JOUR

T1 - Activity of enzalutamide in men with metastatic castration-resistant prostate cancer is affected by prior treatment with abiraterone and/or docetaxel

AU - Cheng, H. H.

AU - Gulati, R.

AU - Azad, A.

AU - Nadal, R.

AU - Twardowski, P.

AU - Vaishampayan, U. N.

AU - Agarwal, N.

AU - Heath, E. I.

AU - Pal, S. K.

AU - Rehman, H. T.

AU - Leiter, A.

AU - Batten, J. A.

AU - Montgomery, R. B.

AU - Galsky, M. D.

AU - Antonarakis, Emmanuel

AU - Chi, K. N.

AU - Yu, E. Y.

PY - 2015/6/14

Y1 - 2015/6/14

N2 - 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.

AB - 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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U2 - 10.1038/pcan.2014.53

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