EORTC-GUCG 1333/PEACE-3 trial

First results of EORTC-GUCG 1333/PEACE-3 trial

Prof Dr Silke Gillessen, a medical oncologist at the EOC – Ospedale Regionale Bellinzona e Valli in Bellinzona, Switzerland, had the distinction of presenting the Late Breaking Abstract 1 as a potentially practice-changing study at the presidential session. The presented data derived from the PEACE-3 trial, a cooperative study involving EORTC, CTI, CUOG, LACOG, and UNICANCER. This trial aimed to evaluate whether the combination of enzalutamide with six cycles of Ra223 offers an advantage in cancer progression compared to enzalutamide monotherapy in the first-line treatment of mCRPC patients with bone metastasis. The primary endpoint of the study was rPFS as assessed by investigators.

An important consideration during the PEACE-3 trial was the release of data from the ERA trial with a similar study design, which reported a significant incidence of fractures in both treatment arms, with a markedly higher fracture rate observed in the combination therapy arm. In response, the PEACE-3 protocol was amended to require the use of bone-protecting agents, and patients with pre-existing osteoporosis were excluded from further participation.

The implications of the PEACE-3 trial data in current clinical practice must be considered within the context of a rapidly evolving treatment landscape for prostate cancer. In the trial, the majority of patients received ADT alone in the mHSPC setting, with around 30% having received ADT plus docetaxel, and only a small number having been treated with abiraterone or another ARPI. However, in today’s clinical setting, most patients with mHSPC receive a hormonal doublet regimen, typically ADT in combination with an ARPI. This shift in practice means that many current patients do not perfectly align with the original PEACE-3 study population. Nonetheless, there remains a subset of patients who continue to receive ADT alone, based on real-world evidence. For these patients, the enzaluatamide-Ra223 combination may represent an attractive first-line option for treating mCRPC patients with bone metastases.