Abstract 492TiP
Background
Screening for HER2-positive tumors with immunohistochemistry (IHC) and in-situ hybridization (ISH) in patients with gastric and esophageal adenocarcinoma and subsequent treatment of HER2-positive patients is part of ESMO guidelines and clinical routine in many countries. However, knowledge about the role of HER2 in patients with squamous cell esophageal cancer (ESCC) is very limited. In a meta-analysis, we have reported that around 9% of 1500 patients with ESCC are HER2 positive. However, there are no published trials examining HER2-directed therapy in this patient population.
Trial design
The HERES trial is a single-arm two-staged, phase II, national multicenter trial that investigates the addition of HER2-directed therapy with trastuzumab in combination with fluoropyrimidine/platinum doublet and pembrolizumab as first-line treatment for HER2-positive ESCC patients. To enable identification of eligible patients, we have implemented national HER2 IHC and ISH reflex screening on all ESCC patients in Denmark while the study is ongoing. The primary endpoint of the study is the rate of 6-month progression free survival (PFS). A 6-month PFS rate of 55 % is considered promising and clinically relevant. If 6-month PFS according to RECIST 1.1 is observed in 7/17 patients in stage 1, accrual of 7 evaluable patients will continue in stage 2. Exploratory endpoints include the correlation of genomic alterations with treatment efficacy, the utilization of circulating tumor DNA as a monitoring tool, and the predictive value of germline Fc Gamma Receptor polymorphisms. The trial was initiated in 2022, is ongoing and has included 11 patients. †Author is deceased
Clinical trial identification
NCT05170256.
Legal entity responsible for the study
Morten Mau-Sørensen.
Funding
The study is an investigator-initiated study. This study has been financially supported by the Danish Comprehensive Cancer Center and the Danish Cancer Society. Expenses for HER2 screening are supported by Roche Diagnostics.
Disclosure
K. Egebjerg: Financial Interests, Personal, Invited Speaker: Astellas Pharma; Financial Interests, Personal, Other, Travel Expenses: AstraZeneca. All other authors have declared no conflicts of interest.