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

*Corresponding author for this work

Research output: Contribution to journalArticle

28 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)2639-2646
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number25
DOIs
Publication statusPublished - 1 Sep 2018

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.

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