Abstract
The treatment landscape for advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma has rapidly evolved over the last decade. The introduction of human epidermal growth factor receptor-2 (HER2)-targeted therapies and immune checkpoint inhibitors in combination with chemotherapy has led to significant improvements in overall survival in biomarker-selected patient populations. The recent Food and Drug Administration approval of zolbetuximab for patients with HER2-negative and Claudin-18 isoform 2 (CLDN18.2)-positive advanced or inoperable GEJ/gastric adenocarcinoma has introduced further complexity into frontline therapy decisions in the absence of direct head-to-head comparisons. Here, we review data from GLOW and SPOTLIGHT trials and discuss key tumor and patient characteristics and propose a therapeutic algorithm to help guide frontline treatment decisions for patients with advanced GEJ and gastric adenocarcinoma in light of the availability of zolbetuximab.