Bayer's XOFIGO Plus Enzalutamide Reduces Death Risk by 24% in Metastatic Prostate Cancer Trial
Key Insights
The Phase III PEACE-3 trial demonstrated that XOFIGO (radium-223 dichloride) combined with enzalutamide reduced the risk of death by 24% compared to enzalutamide alone in men with metastatic castration-resistant prostate cancer (search) and bone metastases (search).
Patients receiving the combination therapy achieved a median overall survival of 38.2 months versus 32.6 months with enzalutamide monotherapy, representing a 5.6-month improvement.
The combination treatment showed increased serious adverse events (69% vs 58% Grade 3 or higher), though no individual severe adverse event increased by more than 5% compared to enzalutamide alone.
Final results from the pivotal Phase III PEACE-3 trial demonstrate that first-line treatment with XOFIGO (radium-223 dichloride) in combination with enzalutamide resulted in a significant overall survival benefit, reducing the risk of death by 24% versus enzalutamide alone in men with metastatic castration-resistant prostate cancer (search) (mCRPC) and bone metastases (search). The hazard ratio was 0.76 (95% confidence interval 0.60-0.96; p=0.0096), with median overall survival reaching 38.2 months (95% CI 33.1-44.8) for the combination versus 32.6 months (95% CI 29.3-38.2) for enzalutamide alone.
Trial Design and Patient Population
The PEACE-3 trial is an international, randomized, open-label, Phase III study that enrolled 446 asymptomatic or mildly symptomatic patients with mCRPC and at least two bone metastases (search). Patients were randomized 1:1 to receive either XOFIGO 55 kBq/kg as an intravenous injection monthly for six cycles in combination with enzalutamide 160mg orally daily, or enzalutamide 160mg orally daily alone.
The primary endpoint was radiological progression-free survival (rPFS) by investigator assessment, with key secondary endpoints including overall survival, time to subsequent systemic treatment, pain progression, and symptomatic skeletal events.
Building on Primary Analysis Success
These final overall survival results build on the primary analysis, which showed a significant improvement in the primary endpoint of radiological progression-free survival with the combination versus enzalutamide alone (19.4 vs. 16.4 months respectively; HR 0.69; 95% CI 0.54–0.87; p=0.0009).
"Despite recent advances in prostate cancer care, many men with mCRPC and bone metastases (search) continue to face a poor prognosis and a high risk of disease progression," said Enrique Gallardo, MD, Parc Tauli Hospital Universitari, Sabadell, Spain and First Author and Presenter of the EORTC 1333/PEACE-3 trial. "Results from PEACE-3 show that starting with a combination of radium-223 and enzalutamide, may help support treatment strategies that prioritize bone health."
Safety Profile
Grade 3 or higher treatment emergent adverse events were recorded in 69% of patients in the combination arm versus 58% of patients treated with enzalutamide alone. However, no individual treatment emergent adverse event Grade 3 or higher increased by more than 5% in the combination arm compared to the enzalutamide arm alone.
Clinical Significance and Regulatory Context
The combination represents a potential advancement in first-line treatment for mCRPC patients with bone metastases (search). XOFIGO is currently indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease, but is not approved in this investigational indication in combination with enzalutamide.
"PEACE-3 is a strong example of how academic cooperative research can help advance progress for complex diseases such as metastatic prostate cancer," said Denis Lacombe, Chief Executive Officer, European Organization for Research and Treatment of Cancer (EORTC). "These Phase III data provide important insights for clinicians and underline the value of international collaboration in generating evidence that supports clinical decision-making."
Radiopharmaceutical Market Context
The success of XOFIGO in combination therapy reflects the growing importance of radioligand therapies in oncology. GlobalData predicts that radiopharmaceuticals within prostate cancer alone will generate $6.3 billion in sales by 2030, driven primarily by expanding treatment applications and market uptake.
The PEACE-3 trial represents a collaboration between several cancer cooperative groups including the European Organization for Research and Treatment of Cancer (EORTC), Clinical Trial Ireland (CTI), the Canadian Urological Oncology Group (CUOG), the Latin American Cooperative Oncology Group (LACOG), and French UNICANCER Urogenital Tumor Study Group (GETUG). The trial is supported by Astellas and Pfizer, who manufacture enzalutamide, in collaboration with Bayer.