Alkaline Phosphatase and Prostate-specific Antigen Response in Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide Alone or in Combination with Radium-223: Ad Hoc Analysis of the PEACE-3 Consortium Trial.

Abstract

Design, setting, and participantsExploratory post hoc analysis of the international, randomised, open-label phase 3 PEACE-3 trial including 446 patients with asymptomatic or mildly symptomatic mCRPC and bone metastases. Overall, 441 and 436 patients were evaluable for ALP and PSA, respectively.InterventionEnzalutamide 160 mg daily alone or combined with six-monthly injections of radium-223 (55 kBq/kg).Outcome measurements and statistical analysisALP response was defined as a ≥30% decline from baseline (ALP-30), and PSA response as a≥50% decline (PSA-50) or ≥90% decline (PSA-90). Confirmed responses required consecutive measurements ≥21 d apart. Time-to-event endpoints were analysed using Kaplan-Meier and Cox models.Results and limitationsAt 6 months, confirmed ALP-30 response was 56.5% with the combination versus 50.8% with enzalutamide alone. Median time to confirmed ALP-30 response was 2.4 versus 3.7 months (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.12-1.78; p = 0.003), and time to ALP normalisation was 2.0 versus 4.5 months (HR 2.05, 95% CI 1.46-2.88; p ConclusionsAdding radium-223 to enzalutamide was associated with faster and more frequent ALP and deep PSA responses. These findings support additional antitumour activity of radium-223 when combined with enzalutamide.