Eur Urol Oncol. 2026 Aug 28:S2588-9311(26)00228-2. doi: 10.1016/j.euo.2026.08.001. Online ahead of print.
ABSTRACT
DESIGN, SETTING, AND PARTICIPANTS: Exploratory 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.
INTERVENTION: Enzalutamide 160 mg daily alone or combined with six-monthly injections of radium-223 (55 kBq/kg).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: ALP 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 LIMITATIONS: At 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 < 0.001). Confirmed PSA-90 response at 6 months was 50.5% versus 34.1% (p = 0.001), with median time to confirmed PSA-90 response of 5.6 versus 22.1 months (HR 1.48, 95% CI 1.13-1.93; p = 0.004). Limitations include the exploratory post hoc design, the absence of multiplicity adjustment, and the lack of an analysis linking biomarker responses to clinical outcomes.
CONCLUSIONS: Adding 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.
PMID:42665513 | DOI:10.1016/j.euo.2026.08.001
