Key clinical point: When prostate-specific antigen levels rise in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer, combining enzalutamide with abiraterone acetate and prednisone in not indicated as it results in more adverse events without therapeutic advantage.
Major finding: 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. Adverse events were more prevalent in the combination group than the control group: Grade 3 hypertension (10% vs. 2%) and increased ALT (6% vs. 2%) or AST (2% v 0%), respectively.
Study details: PLATO (NCT01995513) used a randomized, double-blind, placebo-controlled design. 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.
Disclosures: The study was supported by Medivation, a Pfizer company, and Astellas Pharma, which also funded medical writing and editorial support. Dr. Attard is a consultant to Astellas and Medivation, as well as various other drug companies.
Source: Attard G et al. Journal of Clinical Oncology; published online 20 July 2018. http://ascopubs.org/doi/abs/10.1200/JCO.2018.77.9827
Attard G et al. Journal of Clinical Oncology; published online 20 July 2018. http://ascopubs.org/doi/abs/10.1200/JCO.2018.77.9827