Attard G, et al. - Using a randomized, double-blind, placebo-controlled design, experts tested the presumption that enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate in metastatic castration-resistant prostate cancer with rising prostate-specific antigen (PSA). After PSA progression, during treatment with enzalutamide alone, combining enzalutamide with abiraterone acetate and prednisone is not indicated. With combination therapy, hypertension and elevated liver enzymes are more frequent.

Methods

• In period one, open-label enzalutamide 160 mg daily was received by men with chemotherapy-naïve metastatic castration-resistant prostate cancer.
• Researchers treated the men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 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).
• Time to PSA progression and PSA response in period two were included in the secondary end points.

Results

• As per data, out of 509 patients enrolled in period one, 251 were randomly assigned in period two.
• In the combination group, median progression-free survival was 5.7 months and in the control group it was 5.6 months (hazard ratio, 0.83; 95% CI, 0.61 to 1.12;P= .22).
• Secondary end points demonstrated no difference.
• Compared to the control group, grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination.