Late Breaking Results from the EORTC 1333/PEACE III phase III trial

Professor Silke Gillessen presented the primary results from EORTC GUCG-1333 (PEACE III), an international, randomised Phase 3 trial designed to test the effect of a combination of enzalutamide, an AR pathway inhibitor (ARPI), with the Radium-223 as first-line treatment for patients with metastatic prostate cancer that no longer responds to androgen deprivation therapy (metastatic castration-resistant prostate cancer, or mCRPC), and who had bone metastases. This trial was a collaboration with several other cancer cooperative groups: Clinical Trial Ireland (CTI), the Canadian Urological Oncology Group (CUOG), the Latin American Cooperative Oncology Group (LACOG), and French UNICANCER cooperative group (GETUG). It took more than eight years to complete from first patient enrolled to the closing of the database.

PEACE-III shows that adding six cycles of Ra223 to enzalutamide as first-line treatment for mCRPC patients significantly improved patient outcome by increasing median progression free survival (the primary endpoint) from 16 to 19 months.

An interim analysis at 80% of events showed also an advantage for enzalutamide+Ra223 in terms of overall survival (OS). Due to non-proportional hazards, this will be tested further in the final OS analysis to confirm and further characterise the result.

PEACE III is the first major Phase 3 trial to suggest that combining an ARPI with another approved medication improves OS considerably. Previous Phase 3 studies that tested combinations of two ARPIs or combining an ARPI with a PARP inhibitor have failed to demonstrate a significant OS in the intent-to-treat population.

Toxicity from the treatment was mild, though the trial did illustrate the importance of giving bone protecting agents to avoid fractures. Given the improved efficacy and acceptable toxicity, the researchers say that the combination of enzalutamide and Ra223 can be a new valid treatment option for patients with mCRPC and bone disease and disease progression on androgen deprivation therapy.

Prof Gillessen, Study Chair said: “We found an interesting synergy between Ra223 and enzalutamide and the added toxicity seems manageable”.

Prof Tombal, Study co-Chair said: “PEACE-III gives a new role to Radium 223, much earlier in the disease, that is great news for the patients”.

Denis Lacombe, EORTC’s CEO said: “This groundbreaking trial has the potential to significantly improve patient outcomes. This is precisely the kind of impactful work that EORTC is known for”.

A randomised multicentre open-label phase III trial comparing enzalutamide vs. a combination of radium-223 (223Ra) and enzalutamide in asymptomatic or mildly symptomatic patients with castration-resistant prostate cancer and bone metastases. First results of EORTC-1333/PEACE III

• Presidential Symposium I: Practice-changing trials
  September 14, 2024. 16:30pm – 18:15pm CET
  Presented by Prof. Silke Gillessen on behalf of the PEACE-III investigators

Authors : S. Gillessen¹, A. Choudhury², F. Saad³, E. Gallardo⁴, S. Andrey⁵, Y. Loriot⁶, R.S. McDermott⁷, A.Rodriguez-Vida⁸, P. Isaacson⁹, F. Nolè¹⁰, F. Melo Cruz¹¹, T. Roumeguere¹², K.G. Daugaard¹³, R.Yamamura¹⁴, F. Lecouvet¹⁵, C. Coens¹⁶, B. Fournier¹⁷, B. Tombal¹⁸;

• ^{1 Medical Oncology Department, EOC – Ospedale Regionale Bellinzona e Valli – Istituto Oncologico della Svizzera Italiana (IOSI), Bellinzona, Switzerland,}
• ^{2 Christie Hospital, The Christie NHS Foundation Trust, Manchester, United Kingdom}
• ^{3 Urology Department, Centre Hospitalier de Universite to Montréal (CHUM), Montreal, Canada,}
• ^{4 Oncology Department, Hospital Universitario Parc Taulí, Sabadell, Spain}
• ^{5 Oncology Dept., Hospital Israelita Albert Einstein (Morumbi) – Pavilhao Vicky e Joseph Safra, Sao Paulo, Brazil}
• ^{6 Cancer Medicine Department, Institut Gustave Roussy, Villejuif, Cedex, France}
• ^{7 Department of Oncology, Tallaght University Hospital, Dublin, Ireland, Dublin, Ireland}
• ^{8 Medical Oncology Department, Hospital del Mar – Parc de Salut Mar, Barcelona, Spain}
• ^{9 Department of Oncology, Hospital Moinhos de Vento, Porto Alegre, Brazil, Porto Alegre, Brazil}
• ^{10 Medical Oncology dept., IEO – Istituto Europeo di Oncologia IRCCS, Milan, Italy}
• ^{11 Medical Oncology, Rede D’Or Sao Luiz, Brasilia, Brazil}
• ^{12 Urology Department, Erasme Hospital – Universite Libre de Bruxelles (ULB), Brussels, Belgium}
• ^{13 Department of Oncology, Rigshospitalet, Copenhagen, Denmark}
• ^{14 Medical Oncology Department, Hospital Beneficencia Portuguesa de Sao Paulo – Mirante, Sao Paulo, Brazil}
• ^{15 Radiology, Cliniques Universitaires Saint-Luc (UCLouvain Saint-Luc), Woluwe-Saint-Lambert, Belgium}
• ^{16 Statistical Department, EORTC AISBL/IVZW – European Organisation for Research and Treatment of Cancer, Brussels, Belgium}
• ^{17 Medical Department, EORTC AISBL/IVZW – European Organisation for Research and Treatment of Cancer, Brussels, Belgium}
• ^{18 Urology Department, Cliniques Universitaires Saint-Luc (UCLouvain Saint-Luc), Woluwe-Saint-Lambert, Belgium}

This trial is supported by an investigator driven clinical trial agreement from Bayer HealthCare Pharmaceuticals Inc. and Astellas Pharma Europe.