Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer: Post-hoc Analysis of Randomised Phase 3 Studies

Joaquim Bellmunt; Thian Kheoh; Margaret K. Yu; Matthew R. Smith; Eric J. Small; Peter F.A. Mulders; Karim Fizazi; Dana E. Rathkopf; Fred Saad; Howard I. Scher; Mary Ellen Taplin; Ian D. Davis; Dirk Schrijvers; Andrew Protheroe; Arturo Molina; Peter De Porre; Thomas W. Griffin; Johann S. De Bono; Charles J. Ryan; Stéphane Oudard

doi:10.1016/j.eururo.2015.10.021

Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer: Post-hoc Analysis of Randomised Phase 3 Studies

Joaquim Bellmunt, Thian Kheoh, Margaret K. Yu, Matthew R. Smith, Eric J. Small, Peter F.A. Mulders, Karim Fizazi, Dana E. Rathkopf, Fred Saad, Howard I. Scher, Mary Ellen Taplin, Ian D. Davis, Dirk Schrijvers, Andrew Protheroe, Arturo Molina, Peter De Porre, Thomas W. Griffin, Johann S. De Bono, Charles J. Ryan, Stéphane Oudard

Medicine - Hematology, Oncology, Transplant

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

22 Scopus citations

Abstract

Background The duration of prior hormonal treatment can predict responses to subsequent therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Objective To determine if prior endocrine therapy duration is an indicator of abiraterone acetate (AA) sensitivity. Design, setting, and participants Post-hoc exploratory analysis of randomised phase 3 studies examining post-docetaxel (COU-AA-301) or chemotherapy-naïve mCRPC (COU-AA-302) patients receiving AA. The treatment effect on overall survival (OS), radiographic progression-free survival (rPFS), and prostate-specific antigen (PSA) response analysed by quartile duration of prior gonadotropin-releasing hormone agonists (GnRHa) or androgen receptor (AR) antagonist. Intervention Patients were randomised to AA (1000 mg, orally once daily) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone. Prior endocrine therapy was GnRHa (COU-AA-301, n = 1127 [94%]; COU-AA-302, n = 1057 [97%], 45.1 mo or 36.7 mo median duration, respectively) and/or orchiectomy (COU-AA-301, n = 78 [7%] COU-AA-302, n = 44 [4%]); castrated patients received prior AR antagonists (COU-AA-301, n = 1015 [85%]; COU-AA-302, n = 1078 [99%], 15.7 mo or 16.1 mo median duration, respectively). Outcome measurements and statistical analysis Cox model was used to obtain hazard ratio and associated 95% confidence interval with statistical inference by log rank statistic. Results and limitations Clinical benefit with AA was observed for OS, rPFS, and PSA response for nearly all quartiles with GnRHa or AR antagonists in both COU-AA-301 and COU-AA-302. In COU-AA-301, patients with a longer duration of prior endocrine therapy tended to have greater AA OS, rPFS, and PSA response benefit, with lead-time chemotherapy bias potentially impacting COU-AA-301 results. Time to castration resistance was not captured. This analysis is limited as a post-hoc exploratory analysis. Conclusions In the COU-AA-301 and COU-AA-302 studies, AA produced clinical benefits regardless of prior endocrine therapy duration in patients with mCRPC. Patient summary Metastatic castration-resistant prostate cancer patients derived clinical benefits with abiraterone acetate regardless of prior endocrine therapy duration.

Original language	English (US)
Pages (from-to)	924-932
Number of pages	9
Journal	European Urology
Volume	69
Issue number	5
DOIs	https://doi.org/10.1016/j.eururo.2015.10.021
State	Published - May 1 2016

Bibliographical note

Funding Information:
Acknowledgments: Writing assistance was provided by Ira Mills, PhD, of PAREXEL and was funded by Janssen Global Services.

Funding Information:
Funding/Support and role of the sponsor: This work was supported by Janssen Research & Development (formerly Ortho Biotech Research & Development, unit of Cougar Biotechnology). Employees of Janssen Research & Development participated in trial design and oversight, data monitoring and collection, data analysis, data interpretation, and writing of the report. The study sponsor was involved in trial design and provided grants to trial sites, but had no involvement in the conduct of the trial. Analyses done by Janssen for this report were funded by Janssen Global Services.

Publisher Copyright:
© 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Keywords

Abiraterone acetate
Androgen receptor antagonists
Gonadotropin-releasing hormone
Prednisone
Prostate cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/j.eururo.2015.10.021

http://europepmc.org/articles/pmc5465643

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Bellmunt, J., Kheoh, T., Yu, M. K., Smith, M. R., Small, E. J., Mulders, P. F. A., Fizazi, K., Rathkopf, D. E., Saad, F., Scher, H. I., Taplin, M. E., Davis, I. D., Schrijvers, D., Protheroe, A., Molina, A., De Porre, P., Griffin, T. W., De Bono, J. S., Ryan, C. J., & Oudard, S. (2016). Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer: Post-hoc Analysis of Randomised Phase 3 Studies. European Urology, 69(5), 924-932. https://doi.org/10.1016/j.eururo.2015.10.021

Bellmunt, J, Kheoh, T, Yu, MK, Smith, MR, Small, EJ, Mulders, PFA, Fizazi, K, Rathkopf, DE, Saad, F, Scher, HI, Taplin, ME, Davis, ID, Schrijvers, D, Protheroe, A, Molina, A, De Porre, P, Griffin, TW, De Bono, JS, Ryan, CJ & Oudard, S 2016, 'Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer: Post-hoc Analysis of Randomised Phase 3 Studies', European Urology, vol. 69, no. 5, pp. 924-932. https://doi.org/10.1016/j.eururo.2015.10.021

@article{2bd49ba531b74970918a06a640db2e69,

title = "Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer: Post-hoc Analysis of Randomised Phase 3 Studies",

abstract = "Background The duration of prior hormonal treatment can predict responses to subsequent therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Objective To determine if prior endocrine therapy duration is an indicator of abiraterone acetate (AA) sensitivity. Design, setting, and participants Post-hoc exploratory analysis of randomised phase 3 studies examining post-docetaxel (COU-AA-301) or chemotherapy-na{\"i}ve mCRPC (COU-AA-302) patients receiving AA. The treatment effect on overall survival (OS), radiographic progression-free survival (rPFS), and prostate-specific antigen (PSA) response analysed by quartile duration of prior gonadotropin-releasing hormone agonists (GnRHa) or androgen receptor (AR) antagonist. Intervention Patients were randomised to AA (1000 mg, orally once daily) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone. Prior endocrine therapy was GnRHa (COU-AA-301, n = 1127 [94%]; COU-AA-302, n = 1057 [97%], 45.1 mo or 36.7 mo median duration, respectively) and/or orchiectomy (COU-AA-301, n = 78 [7%] COU-AA-302, n = 44 [4%]); castrated patients received prior AR antagonists (COU-AA-301, n = 1015 [85%]; COU-AA-302, n = 1078 [99%], 15.7 mo or 16.1 mo median duration, respectively). Outcome measurements and statistical analysis Cox model was used to obtain hazard ratio and associated 95% confidence interval with statistical inference by log rank statistic. Results and limitations Clinical benefit with AA was observed for OS, rPFS, and PSA response for nearly all quartiles with GnRHa or AR antagonists in both COU-AA-301 and COU-AA-302. In COU-AA-301, patients with a longer duration of prior endocrine therapy tended to have greater AA OS, rPFS, and PSA response benefit, with lead-time chemotherapy bias potentially impacting COU-AA-301 results. Time to castration resistance was not captured. This analysis is limited as a post-hoc exploratory analysis. Conclusions In the COU-AA-301 and COU-AA-302 studies, AA produced clinical benefits regardless of prior endocrine therapy duration in patients with mCRPC. Patient summary Metastatic castration-resistant prostate cancer patients derived clinical benefits with abiraterone acetate regardless of prior endocrine therapy duration.",

keywords = "Abiraterone acetate, Androgen receptor antagonists, Gonadotropin-releasing hormone, Prednisone, Prostate cancer",

author = "Joaquim Bellmunt and Thian Kheoh and Yu, {Margaret K.} and Smith, {Matthew R.} and Small, {Eric J.} and Mulders, {Peter F.A.} and Karim Fizazi and Rathkopf, {Dana E.} and Fred Saad and Scher, {Howard I.} and Taplin, {Mary Ellen} and Davis, {Ian D.} and Dirk Schrijvers and Andrew Protheroe and Arturo Molina and {De Porre}, Peter and Griffin, {Thomas W.} and {De Bono}, {Johann S.} and Ryan, {Charles J.} and St{\'e}phane Oudard",

note = "Funding Information: Acknowledgments: Writing assistance was provided by Ira Mills, PhD, of PAREXEL and was funded by Janssen Global Services. Funding Information: Funding/Support and role of the sponsor: This work was supported by Janssen Research & Development (formerly Ortho Biotech Research & Development, unit of Cougar Biotechnology). Employees of Janssen Research & Development participated in trial design and oversight, data monitoring and collection, data analysis, data interpretation, and writing of the report. The study sponsor was involved in trial design and provided grants to trial sites, but had no involvement in the conduct of the trial. Analyses done by Janssen for this report were funded by Janssen Global Services. Publisher Copyright: {\textcopyright} 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.",

year = "2016",

month = may,

day = "1",

doi = "10.1016/j.eururo.2015.10.021",

language = "English (US)",

volume = "69",

pages = "924--932",

journal = "European Urology",

issn = "0302-2838",

publisher = "Elsevier",

number = "5",

}

TY - JOUR

T1 - Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer

T2 - Post-hoc Analysis of Randomised Phase 3 Studies

AU - Bellmunt, Joaquim

AU - Kheoh, Thian

AU - Yu, Margaret K.

AU - Smith, Matthew R.

AU - Small, Eric J.

AU - Mulders, Peter F.A.

AU - Fizazi, Karim

AU - Rathkopf, Dana E.

AU - Saad, Fred

AU - Scher, Howard I.

AU - Taplin, Mary Ellen

AU - Davis, Ian D.

AU - Schrijvers, Dirk

AU - Protheroe, Andrew

AU - Molina, Arturo

AU - De Porre, Peter

AU - Griffin, Thomas W.

AU - De Bono, Johann S.

AU - Ryan, Charles J.

AU - Oudard, Stéphane

N1 - Funding Information: Acknowledgments: Writing assistance was provided by Ira Mills, PhD, of PAREXEL and was funded by Janssen Global Services. Funding Information: Funding/Support and role of the sponsor: This work was supported by Janssen Research & Development (formerly Ortho Biotech Research & Development, unit of Cougar Biotechnology). Employees of Janssen Research & Development participated in trial design and oversight, data monitoring and collection, data analysis, data interpretation, and writing of the report. The study sponsor was involved in trial design and provided grants to trial sites, but had no involvement in the conduct of the trial. Analyses done by Janssen for this report were funded by Janssen Global Services. Publisher Copyright: © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Background The duration of prior hormonal treatment can predict responses to subsequent therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Objective To determine if prior endocrine therapy duration is an indicator of abiraterone acetate (AA) sensitivity. Design, setting, and participants Post-hoc exploratory analysis of randomised phase 3 studies examining post-docetaxel (COU-AA-301) or chemotherapy-naïve mCRPC (COU-AA-302) patients receiving AA. The treatment effect on overall survival (OS), radiographic progression-free survival (rPFS), and prostate-specific antigen (PSA) response analysed by quartile duration of prior gonadotropin-releasing hormone agonists (GnRHa) or androgen receptor (AR) antagonist. Intervention Patients were randomised to AA (1000 mg, orally once daily) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone. Prior endocrine therapy was GnRHa (COU-AA-301, n = 1127 [94%]; COU-AA-302, n = 1057 [97%], 45.1 mo or 36.7 mo median duration, respectively) and/or orchiectomy (COU-AA-301, n = 78 [7%] COU-AA-302, n = 44 [4%]); castrated patients received prior AR antagonists (COU-AA-301, n = 1015 [85%]; COU-AA-302, n = 1078 [99%], 15.7 mo or 16.1 mo median duration, respectively). Outcome measurements and statistical analysis Cox model was used to obtain hazard ratio and associated 95% confidence interval with statistical inference by log rank statistic. Results and limitations Clinical benefit with AA was observed for OS, rPFS, and PSA response for nearly all quartiles with GnRHa or AR antagonists in both COU-AA-301 and COU-AA-302. In COU-AA-301, patients with a longer duration of prior endocrine therapy tended to have greater AA OS, rPFS, and PSA response benefit, with lead-time chemotherapy bias potentially impacting COU-AA-301 results. Time to castration resistance was not captured. This analysis is limited as a post-hoc exploratory analysis. Conclusions In the COU-AA-301 and COU-AA-302 studies, AA produced clinical benefits regardless of prior endocrine therapy duration in patients with mCRPC. Patient summary Metastatic castration-resistant prostate cancer patients derived clinical benefits with abiraterone acetate regardless of prior endocrine therapy duration.

AB - Background The duration of prior hormonal treatment can predict responses to subsequent therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Objective To determine if prior endocrine therapy duration is an indicator of abiraterone acetate (AA) sensitivity. Design, setting, and participants Post-hoc exploratory analysis of randomised phase 3 studies examining post-docetaxel (COU-AA-301) or chemotherapy-naïve mCRPC (COU-AA-302) patients receiving AA. The treatment effect on overall survival (OS), radiographic progression-free survival (rPFS), and prostate-specific antigen (PSA) response analysed by quartile duration of prior gonadotropin-releasing hormone agonists (GnRHa) or androgen receptor (AR) antagonist. Intervention Patients were randomised to AA (1000 mg, orally once daily) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone. Prior endocrine therapy was GnRHa (COU-AA-301, n = 1127 [94%]; COU-AA-302, n = 1057 [97%], 45.1 mo or 36.7 mo median duration, respectively) and/or orchiectomy (COU-AA-301, n = 78 [7%] COU-AA-302, n = 44 [4%]); castrated patients received prior AR antagonists (COU-AA-301, n = 1015 [85%]; COU-AA-302, n = 1078 [99%], 15.7 mo or 16.1 mo median duration, respectively). Outcome measurements and statistical analysis Cox model was used to obtain hazard ratio and associated 95% confidence interval with statistical inference by log rank statistic. Results and limitations Clinical benefit with AA was observed for OS, rPFS, and PSA response for nearly all quartiles with GnRHa or AR antagonists in both COU-AA-301 and COU-AA-302. In COU-AA-301, patients with a longer duration of prior endocrine therapy tended to have greater AA OS, rPFS, and PSA response benefit, with lead-time chemotherapy bias potentially impacting COU-AA-301 results. Time to castration resistance was not captured. This analysis is limited as a post-hoc exploratory analysis. Conclusions In the COU-AA-301 and COU-AA-302 studies, AA produced clinical benefits regardless of prior endocrine therapy duration in patients with mCRPC. Patient summary Metastatic castration-resistant prostate cancer patients derived clinical benefits with abiraterone acetate regardless of prior endocrine therapy duration.

KW - Abiraterone acetate

KW - Androgen receptor antagonists

KW - Gonadotropin-releasing hormone

KW - Prednisone

KW - Prostate cancer

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SN - 0302-2838

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JF - European Urology

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ER -

Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer: Post-hoc Analysis of Randomised Phase 3 Studies

Abstract

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Keywords

UN SDGs

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