PERSIAN trial: Early results from a randomized phase II trial testing apalutamide and stereotactic body radiation therapy for low-burden, metastatic, hormone-sensitive prostate cancer.
Authors: Giulio Francolini, Vanessa Di Cataldo, Pietro Garlatti, Saverio Caini, Alessio Bruni, Nicola Simoni, Matteo Augugliaro, Roberto Iacovelli, Luca Tagliaferri, Nicola Battelli, Gianluca Ingrosso, Angelo Porreca, Marco Trovò, Giuseppe Fornarini, Giuseppe Carlo Iorio, Alessia Guarneri, Michele Sisani, Lorenzo Antonuzzo, Alfio Di Grazia, Lorenzo Livi
Journal: Journal of Clinical Oncology (2025)

160 Background: Apalutamide+androgen deprivation therapy (ADT) showed to significantly improve overall survival in low and high volume metastatic hormone sensitive prostate cancer (mHSPC) if compared to ADT alone. However, a randomized phase II trial (ARTO, NCT03449719) suggested that stereotactic body radiotherapy (SBRT) improved clinical outcomes when administered concomitantly with abiraterone acetate in metastatic castration resistance prostate cancer (mCRPC). Nonetheless, evidence related to use of SBRT in addition to androgen receptor pathway inhibitors (ARPIs) in oligometastatic HSPC is currently lacking. PERSIAN trial is aimed to test the hypothesis that metastases directed SBRT will improve outcomes in selected subgroups of patients with oligometastatic mHSPC treated with apalutamide + ADT. Methods: PERSIAN NCT05717660 is a phase II randomized trial enrolling patients affected by metachronous oligometastatic HSPC. Patients with de novo metastatic disease or with &gt; 5 distant metastases are excluded from the trial. All patients are randomized to standard of care with apalutamide+ADT (ARM A: Control) or the same systemic treatment combined with SBRT on all sites of metastatic disease evidenced on conventional imaging (ARM B: Treatment). Here is presented the first interim analysis focused on rate of complete biochemical response (PSA &lt; 0.2 ng/ml) after 3 months since apalutamide + ADT start. Results: Up to date, 174 patients have been enrolled (96.6% of the target sample size), 87 of these reached a minimum follow up of 3 months. Rate of patients with a complete biochemical response was 91.1% vs 92.9% in the control vs treatment arm, respectively (OR 1.27, 95% CI 0.27-6.03, p=0.765). Patients with PSMA positive lesions undetected on conventional imaging vs patients in whom number of target lesions was consistent on conventional and PSMA imaging had similar results (OR 0.74, 95%CI 0.08-6.94, p=0.791). Presence of bone metastatic lesions did not influence rate of complete biochemical response (OR 1.39, 95%CI 0.29-6.67, p-value 0.678). When adjusted for number of lesions, a significant benefit in favour of experimental arm was detected for patients with &lt;3 metastatic sites (OR 5.88, 95%CI 1.13-33.3, p=0.03). Conclusions: Rate of early complete biochemical response showed a non significant trend in favour of experimental arm, with a 27% odds increase in the overall population for patients undergoing SBRT. Clinical benefit of SBRT is significantly improved in patients with lower burden of disease (&lt;3 metastatic lesions). Trial accrual will be completed within the end of 2024, early results about complete biochemical response at 6 months in the complete cohort will be available in the second half of 2025. Clinical trial information: NCT03449719 .