PEACE-3 data for radium-223/enzalutamide published in Annals of Oncology

Results of the EORTC-GUCG 1333/PEACE-3 (NCT02194842) trial were published in the Annals of Oncology today, May 30, 2025, demonstrating that combination enzalutamide (Xtandi) plus radium-223 (Ra223, Xofigo) for the treatment of metastatic castration-resistant prostate cancer with bone metastases is both safe and associated with significantly improved radiological progression-free survival (rPFS).^1,2

Median rPFS was 19.4 months in patients receiving combination Ra223/enzalutamide vs 16.4 months in patients receiving enzalutamide alone.

Specifically, investigators reported that the addition of Ra223 to enzalutamide was associated with a 31% reduction in the risk of progression or death (HR 0.69; 95% CI, 0.54-0.87; P = .0009) compared with enzalutamide alone.¹

Results from PEACE-3 were previously presented as a late-breaking abstract at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain. A total of 446 patients from 12 countries were enrolled from November 2015 to March 2023. Patients were randomly assigned 1:1 to receive either Ra223 55 kBq/kg as an intravenous injection monthly for 6 cycles in combination with enzalutamide 160 mg orally daily or enzalutamide 160 mg orally daily. The primary end point was rPFS by investigator assessment, and key secondary end points included overall survival (OS), time to subsequent systemic treatment, pain progression, and symptomatic skeletal event. Median follow-up was 42.2 months. The trial included collaboration with the European Organization for Research and Treatment of Cancer (EORTC), Clinical Trial Ireland, the Canadian Urological Oncology Group, the Latin American Cooperative Oncology Group, and French UNICANCER Urogenital Tumor Study Group.¹

At the time of the presentation at ESMO 2024, investigator Silke Gillessen, MD, medical oncologist at the Oncology Institute of Southern Switzerland, Bellinzona, commented, “The combination of enzalutamide and 6 cycles of radium-223 shows a statistically significant improvement in rPFS, with a 31% reduction in radiological progression or death…These results support the combination of enzalutamide plus radium-223 plus a bone-protecting agent as a potential new first-line mCRPC treatment option for patients with prostate cancer and bone metastases who have not received a prior androgen receptor pathway inhibitor.”⁴

Median rPFS was 19.4 months in patients receiving combination Ra223/enzalutamide (95% CI: 17.1-25.3 months) vs 16.4 months (95% CI: 13.8-19.2 months) in patients receiving enzalutamide alone. Median OS was 42.3 months (95% CI: 36.8-49.1) for Ra223 plus enzalutamide compared with 35.0 months (95% CI: 28.8-38.9) in the enzalutamide-only group. Bayer reported that, “The study will continue to the final OS analysis.”¹

“There remains an unmet patient need for people living with metastatic castration-resistant prostate cancer who have bone metastases,” said Christine Roth, Global Head of Product Strategy and Commercialization at Bayer’s Pharmaceuticals Division, in a news release about the publication. “The PEACE III trial underscores our dedication to advancing therapies for patients with prostate cancer and exploring the full potential of XOFIGO.”

Denis Lacombe, CEO of EORTC, also commented on the publication of the data, saying, “PEACE III is the first major phase 3 trial to combine an [androgen receptor pathway inhibitor] with radiopharmaceutical that showed statistical significance in meeting the primary endpoint. The EORTC is proud to be at the forefront of this groundbreaking trial, helping to redefine the development of clinical trials and supporting patient care for difficult to treat diseases.”¹

REFERENCES

1. New XOFIGO (radium-223 dichloride) data in metastatic castration-resistant prostate cancer from phase III PEACE III trial published in Annals of Oncology. News release. Bayer. May 30, 2025. Accessed May 30, 2025. https://www.bayer.com/en/us/news-stories/xofigo-data

2. Tombal B, Choudhury A, Saad F, et al. Enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer: Results of the EORTC 1333/PEACE-3 trial. Ann Oncol. May 30, 2025. Accessed May 30, 2025. doi:10.1016/j.annonc.2025.05.011

3. Xofigo (radium-223 dichloride) injection [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, December 2019. Accessed May 30, 2025

4. Gillessen S, Choudhury A, Saad F, et al. A randomized multicenter open label phase III trial comparing enzalutamide vs a combination of radium-223 (Ra223) and enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic castration-resistant prostate cancer (mCRPC): First results of EORTC-GUCG 1333/PEACE-3. Presented at: 2024 European Society for Medical Oncology Annual Congress. September 13-17, 2024. Barcelona, Spain. Abstract LBA1. https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/session/calendar?q=LBA1