Insights From the PEACE III Trial
An expert discusses how the PEACE III trial demonstrated that combining radium-223 with enzalutamide significantly improved radiographic progression-free survival and overall survival compared with enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC) who had bone metastases and limited prior treatment exposure.
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The PEACE III trial represents a groundbreaking advancement in mCRPC treatment, combining radium-223 with enzalutamide for patients with bone metastases. This pivotal study enrolled patients who predominantly received only androgen deprivation therapy (ADT) in the metastatic hormone-sensitive setting, with some having received docetaxel. Importantly, all participants had bone metastases but were asymptomatic or mildly symptomatic, representing a different patient population than traditionally considered for radium therapy.
The study design featured a 1:1 randomization between enzalutamide alone vs enzalutamide plus radium-223, administered in standard dosing cycles every 4 weeks for 6 total treatments. The primary end point focused on radiographic progression-free survival, with secondary end points including overall survival, safety profiles, time to subsequent treatment, and pain progression. All patients were mandated to receive bone health agents, such as zoledronic acid or denosumab, a critical requirement based on lessons learned from previous trials that showed unacceptably high fracture rates without bone protection.
The results demonstrated superior efficacy for the combination therapy, with a hazard ratio of 0.69 for radiographic progression-free survival compared with enzalutamide alone. Overall survival data, though not yet mature, showed promising results with an approximately 7-month improvement and statistical significance. The combination also achieved superior prostate-specific antigen response rates and alkaline phosphatase responses. Although adverse events were more frequent with combination therapy, they were manageable and additive rather than synergistic, establishing this regimen as a new standard of care for appropriately selected patients with mCRPC.
