Rezvilutamide (Rez) versus bicalutamide (Bic) plus androgen-deprivation therapy (ADT) in high-volume, metastatic, hormone-sensitive prostate cancer (mHSPC): 5-year outcomes of the phase 3 CHART trial.

5090 Background: In the CHART trial, Rez plus ADT significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) compared with Bic plus ADT in patients (pts) with high-volume mHSPC (Gu et al., Lancet Oncol 2022). Here, we present updated outcomes ~5 years after the enrollment of the last pt. Methods: Pts with high-volume mHSPC and without previous chemotherapy or other localized treatment for PC were eligible to be enrolled. Pts were randomized 1:1 to receive ADT plus either Rez (240 mg) or Bic (50 mg) orally once daily. Final analysis for OS was planned after 325 deaths were reported. Results: Between Jun 28, 2018, and Aug 6, 2020, 654 pts were randomized to receive Rez plus ADT (n=326) or Bic plus ADT (n=328). As of data cutoff (Jun 6, 2025), with a median follow-up of 72.8 months (IQR 69.1-77.4), there were 141 (43.3%) deaths in Rez plus ADT group and 194 (59.1%) in Bic plus ADT group. OS was improved with Rez plus ADT versus Bic plus ADT (median 78.8 months [95% CI 68.3-not reached (NR)] vs 44.8 months [95% CI 37.1-57.4]; HR 0.59 [95% CI 0.47-0.73]; 2-sided p<0.0001). Risk of progression or death in Rez plus ADT group was reduced by 62% compared with Bic plus ADT group (HR 0.38 [95% CI 0.30-0.48]). Other efficacy outcomes also favored Rez plus ADT (Table). Rez plus ADT improved patient-reported quality of life. No new safety signals were observed. Conclusions: Rez plus ADT continued to show meaningful survival benefits with manageable toxicities after long-term follow-up, further supporting Rez plus ADT as frontline treatment for pts with high-volume mHSPC. Clinical trial information: NCT03520478 . Efficacy endpoints. Rez plus ADT (n=326) Bic plus ADT (n=328) HR (95% CI) 2-sided p-value OS, months 78.8 (68.3-NR) 44.8 (37.1-57.4) 0.59 (0.47-0.73) <0.0001 rPFS per investigator, months 81.0 (62.6-NR) 18.5 (14.8-25.7) 0.38 (0.30-0.48) <0.0001 rPFS per investigator (sensitivity analysis # ), months 58.9 (50.10-NE) 18.6 (16.30-22.90) 0.38 (0.31-0.47) <0.0001 Time to PSA progression, months NR (NR-NR) 11.0 (9.2-12.9) 0.21 (0.17-0.27) <0.0001 Time to next skeletal-related event, months 78.8 (58.9-NR) 37.7 (34.3-48.2) 0.63 (0.51-0.78) <0.0001 Time to initiation of new anti-prostate cancer therapy, months 62.4 (46.4-75.6) 15.1 (13.6-18.1) 0.32 (0.26-0.39) <0.0001 Data are median (95% CI) unless otherwise indicated. # New anti-cancer therapy and missing tumor assessments were not considered. PSA, prostate specific antigen.