Zolbetuximab for gastroesophageal adenocarcinoma: drug review and lessons from the frontlines

Molecular distinctions have started to define treatment decisions in advanced gastric adenocarcinoma (GAC) and gastroesophageal junction adenocarcinoma (GEJAC), malignancies in need of improved outcomes. Claudin 18.2 (CLDN18.2) represents a new selective GAC/GEJAC target, with multiple agents currently in the developmental pipeline. Zolbetuximab, an anti-CLDN18.2 monoclonal antibody, is the first agent to market for this target. It received FDA approval following Phase III trials in which zolbetuximab combined with upfront fluoropyrimidine plus platinum therapy resulted in improved coveted endpoints compared to fluoropyrimidine plus platinum alone in CLDN18.2 positive advanced GAC patients (2+ or 3+ intensity in ≥75% of tumor cells). The most common adverse events are gastrointestinal, primarily nausea and vomiting during initial treatment cycles, particularly in those with an intact stomach (i.e. no prior surgery). Real-world implementation of zolbetuximab is complicated by cumbersome administration times, short drug stability, extended observation time, and difficult tolerability. This report describes our experience in implementing zolbetuximab in clinical practice and provides an extensive drug evaluation.