PERSIAN trial (NCT03449719): Predictive features of complete biochemical response within a randomized phase II trial testing apalutamide and stereotactic body radiation therapy for low-burden, metastatic, hormone-sensitive prostate cancer.

Abstract

157 Background: Apalutamide+androgen deprivation therapy (ADT) currently represents one of the accepted standards of care for systemic treatment for metastatic hormone sensitive prostate cancer (mHSPC). Stereotactic body radiotherapy (SBRT) on top of I line androgen receptor pathway inhibitors (ARPIs) treatment showed to significantly improve radiological progression free survival in castrate resistant setting and PERSIAN trial (NCT05717660) is a randomized phase II trial testing the benefit of concomitant ARPIs and SBRT in mHSPC setting. Methods: Patients affected by metachronous oligometastatic HSPC were 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). Patients affected by de novo metastatic disease or > 5 distant metastases were excluded from the trial. Here is reported an early analysis focusing on rates of complete biochemical response (CBR: defined as PSA< 0.2 ng/ml) and predictive features of CBR at 6 months after treatment start in this population. Results: Sample size was completed in November 2024 after enrollment of 180 patients. Of these, 154 had at least 6 months of follow up data. In the overall population, CBR rate was 93.5%. Neither the presence of PSMA positive lesions undetected on conventional imaging or the presence of bone metastatic lesions affected the rate of CBR (OR 0.33, p=0.13 and OR 1.22, p= 0.77). Conversely, patients with <3 metastatic lesions had significantly improved complete biochemical response rate (OR 0.11, 95% CI 0.03-0.44, p-value 0.002). Conclusions: Rate of CBR was higher in oligometastatic HSPC if compared to unselected mHSPC enrolled in TITAN trial, especially in subgroup of patients with lower disease burden (e.g., < 3 metastatic lesions). This suggests improved outcomes in this population. Further analyses on the final sample size are awaited to explore the impact of SBRT on early and later clinical outcomes in control vs treatment arm. Clinical trial information: NCT03449719 .