Efficacy of rezvilutamide in preventing the flare phenomenon induced by GnRH agonists in newly diagnosed metastatic hormone-sensitive prostate cancer: An exploratory multicenter randomized controlled trial.

191 Background: Current guidelines recommend first-generation antiandrogens ≥7 days before or concomitant with gonadotropin-releasing hormone (GnRH) agonists to prevent transient surges in luteinizing hormone (LH), testosterone, prostate-specific antigen (PSA) and clinical symptoms, known as the flare phenomenon. Data on next-generation androgen receptor inhibitors in this context are limited. This study evaluated the efficacy of rezvilutamide combined with a GnRH agonist in preventing the flare phenomenon in metastatic hormone-sensitive prostate cancer (mHSPC) (Clinical Trial Registration: ChiCTR2300076106). Methods: In this exploratory multicenter randomized trial, 60 patients aged > 18 years with newly diagnosed, histologically confirmed prostate adenocarcinoma and ≥1 distant metastasis, baseline PSA > 2 ng/mL and testosterone > 1.5 ng/mL, were enrolled. Participants were randomized 1:1 to: (1) control, rezvilutamide administered 1 day before GnRH agonist (“1-day regimen”), or (2) experimental, rezvilutamide administered with 1-hour interval relative to GnRH agonist (“1-hour regimen”). Treatment continued until disease progression or intolerable toxicity. PSA, LH, and testosterone were assessed on Days −1 (control only), 0, 1, 3, 7, 14, and 28 post-GnRH administration, with follow-up every 28 days thereafter. Results: Between October 2023 and October 2025, 54 patients from eight centers met eligibility criteria and completed treatment (n = 27 per group). Groups were comparable in age at baseline and in PSA, testosterone, and LH levels on day 0. Median PSA declined rapidly in both groups, with significant reductions from Day 7 (experimental P < 0.05; control P < 0.01) and sustained suppression through Day 84 (experimental: 376.3→0.2 ng/mL, P < 0.01; control: 366.7→0.3 ng/mL, P < 0.01); The experimental group showed greater relative PSA reduction on Days 0, 1, and 3 (P < 0.01). LH peaked on Day 1 (experimental: 34.7 ng/mL; control: 26.6 ng/mL) and testosterone peaked on Day 3 (experimental: 6.3 ng/mL; control: 6.6 ng/mL), declining below baseline by Day 14 (P < 0.01). Relative changes in LH and testosterone were similar between groups at all early time points (Days 0–15). Conclusions: In treatment-naïve mHSPC patients, rezvilutamide, administered either one day before or with a 1-hour interval relative to GnRH agonists, rapidly and durably suppressed PSA and clinical symptoms, effectively preventing the flare phenomenon. Clinical trial information: ChiCTR2300076106 .