# Potential Resistance to Oxaliplatin-Based Regimens in Gastric Cancer Patients with ERBB2 R678Q Mutation: Evidence from a National Genomic Database

## TL;DR

A specific ERBB2 mutation, R678Q, is linked to poor response to oxaliplatin in gastric cancer patients, based on a national genomic database.

## Contribution

The study identifies ERBB2 R678Q as a novel predictor of resistance to oxaliplatin-based therapy in gastric cancer.

## Key findings

- ERBB2 R678Q mutation is associated with lower response rates to oxaliplatin-based regimens.
- No resistance to ramucirumab or nivolumab was observed in R678Q mutation carriers.
- The ERBB2 R678Q mutation may guide treatment decisions in gastric cancer.

## Abstract

Epidermal growth factor receptor 2 (ERBB2/HER2) is a critical biomarker in gastric cancer management, but the clinical implications of specific ERBB2 mutations remain poorly characterized. Methods/Results: We investigated the ERBB2 R678Q mutation, utilizing the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which involved the analysis of 3116 gastric/gastroesophageal junction adenocarcinomas. ERBB2 mutations were identified in 130 cases, with R678Q present in 40 patients. These patients exhibited significantly lower response rates to oxaliplatin-based regimens compared to ERBB2 wild-type cases (19.0% vs. 38.0%, p = 0.03), while other ERBB2 mutations demonstrated no such resistance. No significant differences in the response were observed to the ramucirumab or nivolumab regimens. Conclusions: Our findings suggest that the ERBB2 R678Q mutation may predict a poor response to oxaliplatin-based therapy. This study provides real-world evidence supporting the potential clinical relevance of this specific ERBB2 mutation in treatment decision making for gastric cancer.