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 the 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.
Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2018 Jul 20 [Epub ahead of print]
J Clin Oncol 36:2639-2646. © 2018 by American Society of Clinical Oncology
Authors: Gerhardt Attard, Michael Borre, Howard Gurney, Yohann Loriot, Corina Andresen-Daniil, Ranjith Kalleda, Trinh Pham, Mary-Ellen Taplin, PLATO collaboratorsAuthor Affiliation: Gerhardt Attard, The Institute of Cancer Research and the Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Michael Borre, Aarhus University Hospital, Aarhus, Denmark; Howard Gurney, Macquarie University, Sydney, New South Wales, Australia; Yohann Loriot, Gustave Roussy, Institut National de la Sante et de la Recherche Medicale U981, University of Paris Saclay, ´Villejuif, France; Corina Andresen-Daniil, Ranjith Kalleda, and Trinh Pham, Pfizer, New York, NY; and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA