No Benefit of Adding Abiraterone to Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Increasing PSA
The PLATO trial failed to show benefit of adding abiraterone (Zytiga)/prednisone to ongoing enzalutamide (Xtandi) vs abiraterone/prednisone in men with metastatic castration-resistant prostate cancer exhibiting rising prostate-specific antigen (PSA) during enzalutamide treatment. Results of the trial have been reported in the Journal of Clinical Oncology by Attard et al.
Study Details
The trial enrolled 509 patients from 51 sites in North America, Europe, and Australia. In period 1, these patients received open-label enzalutamide 160 mg daily. Those with no PSA increase at weeks 13 and 21 continued treatment until PSA progression (≥ 25% increase and ≥ 2 ng/mL above nadir) and were then randomized in the double-blind period 2 to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo. A total of 251 patients were randomized to the combination group (n = 126) or control group (n = 125).
The primary endpoint was progression-free survival (radiographic or unequivocal clinical progression or death during study).
Progression-Free Survival
Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio = 0.83, P = .22). Reduction in baseline PSA of ≥ 50% occurred in 1% vs 2% of patients. Median time to PSA progression was 2.8 months in both groups (HR = 0.87, P = .45). No differences between groups were observed in rate of pain progression, objective response rate, or time to first use of subsequent antineoplastic therapy.
Adverse Events
Grade ≥ 3 adverse events occurred in 45% of the combination group vs 37% of the control group, with the most common in the combination group with a higher incidence vs the control group being hypertension (10% vs 2% in control group), increased ALT (6% vs 2%), and increased AST (2% vs 0%).
The investigators concluded, “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.”
The study was supported by Medivation, a Pfizer company, and Astellas Pharma.
Gerhardt Attard, MD, of The University College London Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
