1795P - China ARCHES: A multicenter phase III randomized double-blind placebo (PBO)-controlled efficacy and safety trial of enzalutamide (ENZA) + androgen deprivation therapy (ADT) vs PBO + ADT in Chinese patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC)

Background

In the global ARCHES trial (NCT02677896), ENZA + ADT improved overall survival and radiographic progression-free survival (rPFS) vs PBO + ADT in pts with mHSPC. The China ARCHES trial evaluated the efficacy and safety of ENZA + ADT vs PBO + ADT in Chinese pts with mHSPC.

Methods

Chinese men with mHSPC (positive bone scan or CT scan) were randomized 2:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume and prior docetaxel therapy. Treatment continued until intolerability or confirmed radiographic progression. The primary endpoint was time to prostate-specific antigen (PSA) progression (TTPP; PSA progression defined as ≥25% increase and absolute increase of ≥2 ng/mL above the nadir, confirmed after ≥3 weeks), based on central laboratory test. Selected secondary endpoints included rPFS, time to castration resistance (TTCR), PSA undetectable (<0.2 ng/mL) rate in patients with detectable PSA at baseline, and safety. We report the results of a prespecified interim analysis (63 TTPP events accrued).

Results

At data cut-off (November 18, 2022), 180 pts (ENZA + ADT, n=120; PBO + ADT, n=60) had been randomized from 27 centers in China (median age, 68.5 years). Baseline characteristics were balanced between treatment arms. Median treatment duration with ENZA + ADT vs PBO + ADT was 25.66 vs 15.11 months. Based on 63 centrally confirmed PSA progressions (ENZA + ADT, 23; PBO + ADT, 40), ENZA + ADT significantly reduced the risk of PSA progression by 87% vs PBO + ADT (Table). rPFS, TTCR, and PSA undetectable rate were among the secondary endpoints improved with ENZA + ADT vs PBO + ADT. Safety outcomes in pts from China were consistent with those in the global ARCHES population. Table: 1795P

^aCox proportional hazards model^{h b}Median months: Kaplan-Meier method ^cBrookmeyer and Crowley method ^dLog-rank test^{h e}Nominal p value ^fClopper-Pearson method based on exact binomial distribution ^gCochran-Mantel-Haenszel score test^{h h}Stratified model/test CI=confidence interval; N=no. of randomized pts; NR=not reached.

Conclusions

Efficacy and safety results in China ARCHES were generally consistent with those in the global ARCHES trial.

Clinical trial identification

Editorial acknowledgement

Medical writing and editorial assistance were provided by Marietou Daou, MSc, and Jane Beck, MA, from Complete HealthVizion, IPG Health Medical Communications, funded by the study sponsors.

Legal entity responsible for the study

Astellas Pharma Inc.; Pfizer Inc.

Funding

This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide.

Disclosure

F. Zhou, Z. Gongqian, H. Guo, Z. Hu, D. He, D. Zhang, Y. Li, H. Kadeerbai, Y. Liu, D. Ye: Non-Financial Interests, Institutional, Other, Study funding and support for Medical Writing/editing: Astellas; Non-Financial Interests, Institutional, Other, Medical writing/editing support: Complete HealthVizion. X. Zhang, Z. He: Non-Financial Interests, Institutional, Writing Engagement: Astellas Pharma Inc.