Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment
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¨ıve 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 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