CONFERENCE UPDATE: ESMO 2023
Enzalutamide combined with ADT reduces the risk of disease progression in Chinese men with mHSPC: The China ARCHES trial
STUDY DESIGN
Enzalutamide is a potent oral androgen receptor inhibitor approved for the treatment of castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC).1 In the global ARCHES study, the combined therapy of enzalutamide and androgen deprivation therapy (ADT) exhibited clinically meaningful survival benefits among patients with mHSPC.1 Since then, the China ARCHES trial, an ongoing phase 3 study, has been conducted to compare the efficacy and safety of enzalutamide + ADT with placebo + ADT in Chinese men with mHSPC.1
The China ARCHES study is a multicenter, double-blinded, placebo-controlled, randomized, phase 3 trial that enrolled 180 patients with mHSPC from September 2019 to November 2022.1 The study population was then randomized (2:1) to receive either a daily dose of enzalutamide 160mg + ADT (n=120) or placebo + ADT (n=60) until radiographically confirmed disease progression.1 During the study period, 23 patients from the placebo cohort received open-label enzalutamide + ADT after radiographically confirmed disease progression.1 At the data cutoff, the median duration of treatment with enzalutamide + ADT vs. placebo + ADT was 25.66 months and 15.11 months, respectively.
The primary efficacy endpoint was time to prostate-specific antigen (PSA) progression (TTPP) and the selected secondary endpoints were radiographic progress-free survival (rPFS), time to first symptomatic skeletal event (SSE), time to castration resistance (TTCR), time to initiation of a new antineoplastic therapy, PSA undetectable rate, and overall response rate (ORR).1 Interim safety analysis results were also presented.
FINDINGS
| Primary endpoint: |
| The primary endpoint was TTPP1 |
| Enzalutamide + ADT demonstrated a significant reduction in PSA progression risk of 87% compared with placebo + ADT (HR=0.130; 95% CI: 0.076-0.222; p<0.0001)1 |
| The PSA risk reduction benefit induced by enzalutamide + ADT was maintained in the prespecified sensitivity and subgroup analyses1 |
| Secondary endpoints: |
| The secondary endpoints were rPFS, time to first SSE, TTCR, time to initiation of a new antineoplastic therapy, PSA undetectable rate, and ORR1 |
| Patients who received enzalutamide + ADT experienced significant improvements in rPFS (HR=0.330; 95% CI: 0.196-0.556; p<0.0001), TTCR (HR=0.172; 95% CI: 0.107-0.276; p<0.0001), and PSA undetectable rate (difference=53.5%; 95% CI: 40.1-66.9; p<0.0001) compared to those who received placebo + ADT1 |
| There were no statistically significant differences in the time to initiation of a new antineoplastic therapy, SSE, and ORR between the 2 cohorts1 |
| Safety: |
| The incidence of TEAEs were similar between the 2 cohorts (100% vs. 96.6%). A higher proportion of patients treated with enzalutamide + ADT experienced Grade 3 or 4 TEAEs (52.1% vs. 39.0%) and serious TEAEs (35.3% vs. 20.3%) compared to the placebo + ADT cohort1 |
| The most common TEAEs included musculoskeletal events (31.1% vs. 25.4%), hypertension (27.7% vs. 32.2%), fatigue (21.0% vs. 13.6%), and fractures (12.6% vs. 6.8%)1 |
| The enzalutamide + ADT cohort also had a higher incidence in TEAEs leading to dose reduction (5.0% vs. 3.4%), dose interruption (16.0% vs. 8.5%), and treatment discontinuation (5.0% vs. 3.4%) compared to the placebo + ADT cohort1 |
| Overall, the mortality rate of the placebo + ADT cohort was slightly higher than that of the enzalutamide + ADT cohort (20.3% vs. 17.6%)1 |
"These findings suggest that enzalutamide + ADT is an efficacious and well-tolerated treatment option for Chinese men with mHSPC"
Dr. Gongqian Zeng
Department of Urology,
Hunan Cancer Hospital,
Changsha, China
