A prospective, multicenter, observational study of trastuzumab deruxtecan in elderly patients with HER2-positive gastric cancer: EN-COURAGE

Abstract

Gastric cancer (GC) disproportionately affects the elderly, yet pivotal trials have provided inconsistent evidence regarding the efficacy of human epidermal growth factor receptor 2 (HER2)-targeted and immune-based therapies in this subgroup. Beyond chronological age, geriatric assessment (GA) and sarcopenia measures such as the psoas muscle index (PMI) may better capture vulnerability and predict treatment outcomes. Thus, there is a need for prospective studies specifically designed for elderly patients, incorporating GA and sarcopenia measures.

EN-COURAGE is a prospective, multicenter, observational study evaluating trastuzumab deruxtecan (T-DXd) in patients aged ≥70 years with HER2-positive unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma in Japan. Eligible patients receive T-DXd intravenously at the approved dose and schedule, with dose modifications and treatment interruptions per clinical practice. The target enrollment is 100 patients. The primary endpoint is overall survival (OS); secondary endpoints include progression-free survival (PFS), time to treatment failure (TTF), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), time to treatment discontinuation (TTD), T-DXd treatment status, and safety. A key feature is the systematic integration of GA tools (Geriatric-8, Cancer and Aging Research Group toxicity score) and PMI analysis to explore efficacy and tolerability predictors. EN-COURAGE represents the first prospective study designed to elucidate real-world T-DXd outcomes in elderly patients with HER2-positive GC.