Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment

Gerhardt Attard, Michael Borre, Howard Gurney, Yohann Loriot, Corina Andresen-Daniil, Ranjith Kalleda, Trinh Pham, Mary Ellen Taplin, on behalf of PLATO collaborators, E. Abdi, S. Begbie, I. Davis, A. Guminski, A. Hayden, P. Mainwaring, G. Marx, F. Parnis, D. Pook, J. Shapiro, M. Stockler & 35 others C. Underhill, H. Woo, B. Tombal, H. Van Poppel, P. Werbrouck, M. Borre, P. Iversen, P. Ostri, K. Taari, T. Tammela, M. Vaarala, Y. Loriot, U. De Giorgi, R. Passalacqua, G. Scagliotti, C. Sternberg, V. Balaz, M. Brezovky, F. Goncalves, J. Kliment, A. Alcaraz, M. Domenech Santasusana, A. Font, E. Gallardo, M. A. Gonzalez del Alba Baamonde, M. Guix Arnau, D. Olmos Hidalgo, O. Andren, A. Bjartell, J. E. Damber, P. Hoskin, H. Payne, A. Protheroe, J. Tanguay, R. Given

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Purpose: Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO (ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design. Patients and Methods: In period one, men with chemotherapy-naïve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression ($ 25% increase and $ 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two. Results: Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group. Conclusion: Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy.

LanguageEnglish
Pages2639-2646
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number25
DOIs
Publication statusPublished - 1 Sep 2018

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Castration
Prostate-Specific Antigen
Prostatic Neoplasms
Prednisone
Control Groups
Disease-Free Survival
Placebos
Hypertension
Therapeutics
Androgens
Disease Progression
abiraterone
MDV 3100
Drug Therapy
Liver
Enzymes
Abiraterone Acetate

Bibliographical note

Copyright the American Society of Clinical Oncology 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Cite this

Attard, Gerhardt ; Borre, Michael ; Gurney, Howard ; Loriot, Yohann ; Andresen-Daniil, Corina ; Kalleda, Ranjith ; Pham, Trinh ; Taplin, Mary Ellen ; on behalf of PLATO collaborators. / Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 25. pp. 2639-2646.
@article{597d820d294d4932b5f66c53f30917a3,
title = "Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment",
abstract = "Purpose: Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO (ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design. Patients and Methods: In period one, men with chemotherapy-na{\"i}ve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression ($ 25{\%} increase and $ 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two. Results: Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95{\%} CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10{\%} v 2{\%}) and increased ALT (6{\%} v 2{\%}) or AST (2{\%} v 0{\%}) were more frequent in the combination than the control group. Conclusion: Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy.",
author = "Gerhardt Attard and Michael Borre and Howard Gurney and Yohann Loriot and Corina Andresen-Daniil and Ranjith Kalleda and Trinh Pham and Taplin, {Mary Ellen} and {on behalf of PLATO collaborators} and E. Abdi and S. Begbie and I. Davis and A. Guminski and A. Hayden and P. Mainwaring and G. Marx and F. Parnis and D. Pook and J. Shapiro and M. Stockler and C. Underhill and H. Woo and B. Tombal and {Van Poppel}, H. and P. Werbrouck and M. Borre and P. Iversen and P. Ostri and K. Taari and T. Tammela and M. Vaarala and Y. Loriot and {De Giorgi}, U. and R. Passalacqua and G. Scagliotti and C. Sternberg and V. Balaz and M. Brezovky and F. Goncalves and J. Kliment and A. Alcaraz and {Domenech Santasusana}, M. and A. Font and E. Gallardo and {Gonzalez del Alba Baamonde}, {M. A.} and {Guix Arnau}, M. and {Olmos Hidalgo}, D. and O. Andren and A. Bjartell and Damber, {J. E.} and P. Hoskin and H. Payne and A. Protheroe and J. Tanguay and R. Given",
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Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment. / Attard, Gerhardt; Borre, Michael; Gurney, Howard; Loriot, Yohann; Andresen-Daniil, Corina; Kalleda, Ranjith; Pham, Trinh; Taplin, Mary Ellen; on behalf of PLATO collaborators.

In: Journal of Clinical Oncology, Vol. 36, No. 25, 01.09.2018, p. 2639-2646.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment

AU - Attard, Gerhardt

AU - Borre, Michael

AU - Gurney, Howard

AU - Loriot, Yohann

AU - Andresen-Daniil, Corina

AU - Kalleda, Ranjith

AU - Pham, Trinh

AU - Taplin, Mary Ellen

AU - on behalf of PLATO collaborators

AU - Abdi, E.

AU - Begbie, S.

AU - Davis, I.

AU - Guminski, A.

AU - Hayden, A.

AU - Mainwaring, P.

AU - Marx, G.

AU - Parnis, F.

AU - Pook, D.

AU - Shapiro, J.

AU - Stockler, M.

AU - Underhill, C.

AU - Woo, H.

AU - Tombal, B.

AU - Van Poppel, H.

AU - Werbrouck, P.

AU - Borre, M.

AU - Iversen, P.

AU - Ostri, P.

AU - Taari, K.

AU - Tammela, T.

AU - Vaarala, M.

AU - Loriot, Y.

AU - De Giorgi, U.

AU - Passalacqua, R.

AU - Scagliotti, G.

AU - Sternberg, C.

AU - Balaz, V.

AU - Brezovky, M.

AU - Goncalves, F.

AU - Kliment, J.

AU - Alcaraz, A.

AU - Domenech Santasusana, M.

AU - Font, A.

AU - Gallardo, E.

AU - Gonzalez del Alba Baamonde, M. A.

AU - Guix Arnau, M.

AU - Olmos Hidalgo, D.

AU - Andren, O.

AU - Bjartell, A.

AU - Damber, J. E.

AU - Hoskin, P.

AU - Payne, H.

AU - Protheroe, A.

AU - Tanguay, J.

AU - Given, R.

N1 - Copyright the American Society of Clinical Oncology 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Purpose: Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO (ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design. Patients and Methods: In period one, men with chemotherapy-naïve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression ($ 25% increase and $ 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two. Results: Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group. Conclusion: Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy.

AB - Purpose: Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO (ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design. Patients and Methods: In period one, men with chemotherapy-naïve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression ($ 25% increase and $ 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two. Results: Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group. Conclusion: Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy.

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U2 - 10.1200/JCO.2018.77.9827

DO - 10.1200/JCO.2018.77.9827

M3 - Article

VL - 36

SP - 2639

EP - 2646

JO - Journal of Clinical Oncology

T2 - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 1527-7755

IS - 25

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