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; E. S. Antonarakis; K. N. Chi; E. Y. Yu

doi:10.1038/pcan.2014.53

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, E. S. Antonarakis, K. N. Chi, E. Y. Yu

Research output: Contribution to journal › Article › peer-review

67 Scopus citations

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	https://doi.org/10.1038/pcan.2014.53
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.

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10.1038/pcan.2014.53

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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, E. S., Chi, K. N., & Yu, E. Y. (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, 18(2), 122-127. https://doi.org/10.1038/pcan.2014.53

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, E. S.; 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 journal › Article › peer-review

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, ES, 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, E. S. ; 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.

@article{7a1604ac65ae43d694d50f684bda7be6,

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

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 Antonarakis, {E. S.} and Chi, {K. N.} and Yu, {E. Y.}",

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: {\textcopyright} 2015 Macmillan Publishers Limited All rights.",

year = "2015",

month = jun,

day = "14",

doi = "10.1038/pcan.2014.53",

language = "English (US)",

volume = "18",

pages = "122--127",

journal = "Prostate Cancer and Prostatic Diseases",

issn = "1365-7852",

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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, E. S.

AU - Chi, K. N.

AU - Yu, E. Y.

N1 - 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.

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

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