Randomized phase III trial with a factorial design assessing the efficacy and safety of darolutamide and stereotactic dose-escalated radiotherapy in patients with high-risk localized prostate cancer: the PEACE 7 (GETUG-AFU 45) study protocol

Approximately 15% of patients with localized prostate cancer harbor high risk features. Nowadays, the standard of care for such patients is the combination of androgen deprivation therapy (ADT) plus radiotherapy (hypofractionated or conventional dose escalated radiotherapy). A subset of men still develops metastatic disease despite treatment and additional therapeutic strategies need to be assessed. Recent data support the evaluation of next generation hormonal therapy such as darolutamide and stereotactic body radiotherapy (SBRT) for localized high-risk prostate cancer to improve outcomes. PEACE 7 is an international, multicenter, randomized, open-label phase III trial, which aims to assess the efficacy and safety of darolutamide and SBRT through a 2 × 2 factorial design. Patients included are adult men diagnosed with high-risk prostate cancer (i.e., at least two of the following criteria: Gleason score ≥ 8, T3 or T4 disease, prostate-specific antigen ≥ 20 ng/mL) and with no detectable metastasis on PSMA PET/CT scan. In total, 700 patients are planned to be enrolled over 3 years to demonstrate the efficacy of darolutamide and prostate-targeted SBRT boost, in combination with ADT and prostate and pelvic nodal radiotherapy. Patients are randomized 1:1:1:1 to standard Arm A (standard treatment: ADT + prostate and pelvic moderate hypofractionated or conventional dose-escalated normo-fractionated radiotherapy), experimental Arm B (standard treatment + darolutamide), experimental Arm C (standard treatment + prostate SBRT Boost), or experimental Arm D (standard treatment + prostate SBRT boost+ darolutamide). The randomization is stratified on the number of high-risk factors (2 or 3), the presence of a dominant intra-prostatic lesion (PI-RADS 5, Yes or No), and center. The primary endpoint is metastasis-free survival (MFS) with targeted hazard ratio (HR) of 0.65; 170 events will be required to achieve 80% power at a 2-sided significance level of 5%. Secondary endpoints include clinical progression-free survival, biochemical progression-free survival, time to local relapse, overall survival, prostate cancer-specific survival, acute and long-term toxicity, and quality of life. The PEACE 7 study is the first study to evaluate the effect of darolutamide and dose escalation with SBRT boost, which could change the current management of localized high-risk prostate cancer patients. 2023-509787-15-00 (EuCT); NCT06625970 (ClinicalTrials.gov Identifier).