安可坦在亞洲族群於不同給藥時期的安全性與有效性-ARCHES的事後分析研究

李建儀,¹ 張延驊,²蒲永孝,³ Andrew Armstrong,⁴ Arun Azad,⁵ Arnulf Stenzl,⁶陳宥芳,⁷ Matt Rosales,⁸ Arti Dhar,⁹張慧貞,⁷陳可玫,⁷馮思中¹⁰

¹台中榮民總醫院, 台中,台灣; ²台北榮民總醫院, 台北,台灣; ³台大醫學院附設醫院, 台北, , 台灣; ⁴Duke Department of Medicine, Durham, NC, USA; ⁵Peter MacCallum Cancer Centre, Melbourne Australia; ⁶Eberhard Karls University of Tübingen, Tübingen, Germany; ⁷Astellas Pharma, Inc., Taiwan; ⁸Astellas Pharma, Inc. Northbrook, IL, USA; ⁹Oncology, Astellas Pharma Singapore Pte. Ltd., Singapore, Republic of Singapore; ¹⁰林口長庚紀念醫院, 醫學院, 長庚大學, 桃園, 台灣

Safety and Efficacy of Enzalutamide by Treatment Duration in the Asian Subgroup From ARCHES: A Post Hoc Analysis

Jian-Ri Li,¹ Yen-Hwa Chang,² Yeong-Shiau Pu,³ Andrew Armstrong,⁴ Arun Azad,⁵ Arnulf Stenzl,⁶ Yu-Fang Chen,⁷ Matt Rosales,⁸ Arti Dhar,⁹ Hui-Chen Chang,⁷ Ko-mei Chen,⁷ See-Tong Pang¹⁰

¹Taichung Veterans General Hospital, Taichung; ²Taipei Veterans General Hospital, Taipei, Taiwan; ³College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan; ⁴Duke Department of Medicine, Durham, NC, USA; ⁵Peter MacCallum Cancer Centre, Melbourne Australia; ⁶Eberhard Karls University of Tübingen, Tübingen, Germany; ⁷Astellas Pharma Inc., Taiwan; ⁸Astellas Pharma Inc., Northbrook, IL, USA; ⁹Oncology, Astellas Pharma Singapore Pte. Ltd., Singapore, Republic of Singapore; ¹⁰Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan

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ABSTRACT

Purpose: The phase 3 ARCHES trial (NCT02677896) demonstrated reduced risk of radiographic disease progression or death with enzalutamide (ENZA) + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT with no unexpected adverse events (AEs) in patients (pts) with metastatic hormone-sensitive prostate cancer. This post hoc analysis evaluated the safety of ENZA + ADT over time and efficacy by treatment duration in the ARCHES Asian subgroup.

Materials and Methods: The primary endpoint of this analysis was the rate of AEs of special interest (AESIs) during 0–6, >6–12, and >12–24 mo. Secondary endpoints were median time to ≥90% reduction in prostate-specific antigen level (PSA90), pts with undetectable PSA levels at 6, 12, and 24 mo, radiographic progression-free survival (rPFS) at 6, 12, 18, and 24 mo, subgroup analysis of rPFS, and overall survival (OS).

Results: Data cutoff was October 18, 2018; the cutoff for OS was May 28, 2021. In the Asian subgroup (N=147; ENZA + ADT, n=69; PBO + ADT, n=78), most pts had high disease volume (67%) and Gleason score ≥8 (91%); few had radical prostatectomy (3%) or bilateral orchiectomy (5%). Overall AESI rates with ENZA + ADT vs PBO + ADT during 0–6, >6–12, and >12–24 mo were 52% vs 28%, 17% vs 15%, and 13% vs 5%, respectively. The most common AESIs with ENZA + ADT were musculoskeletal events (15%); fatigue (13%) and hypertension (9%) were most frequent during 0–6 mo with ENZA + ADT. Fracture, falls, convulsion, and cognitive/memory impairment were rare, with similar rates across arms. Median time to reach PSA90 was shorter with ENZA + ADT vs PBO + ADT (2.6 mo vs not reached [NR]; log-rank P<0.0001). With ENZA + ADT, 49% of pts had undetectable PSA levels and all responses were sustained through wk 97. With PBO + ADT, 10% of pts had undetectable PSA levels; no sustained responses were observed. Higher proportions of pts had rPFS with ENZA + ADT vs PBO + ADT at 6 (92% vs 90%), 12 (87% vs 75%), and 18 mo (79% vs 47%). Median rPFS was NR with ENZA + ADT vs 16.8 mo with PBO + ADT. ENZA + ADT reduced risk of radiographic disease progression by 67% (HR, 0.33; log-rank P=0.0083) and increased rPFS across all subgroups (HR, 0.42; 95% CI, 0.19–0.95). Median OS was NR in either group (HR, 0.61; 95% CI, 0.29–1.32; median f/u, 45.9 mo).

Conclusion: In the ARCHES Asian subgroup, AESIs peaked within 6 mo of treatment and rapidly declined thereafter. With ENZA + ADT, median time to reach PSA90 was 2.6 mo, with sustained PSA reduction and improved rPFS. These results support the long-term safety and efficacy of ENZA + ADT in Asian pts.

Presenter phone number or email: fisherfishli@yahoo.com.tw 

Category: Tumor

Funding: This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide. Medical writing/editorial support were provided by Kalpana Vijayan, PhD, and Cheryl Casterline, MA, from OPEN Health Scientific Communications and funded by the study sponsors.