Characterization of early-onset gastritis during zolbetuximab-containing chemotherapy in CLDN18.2-positive gastric cancer

Zolbetuximab, a monoclonal antibody targeting claudin 18.2 (CLDN18.2), plus chemotherapy has become a standard treatment for CLDN18.2-positive advanced gastric cancer and is frequently associated with early-onset gastrointestinal (GI) toxicities. While zolbetuximab-induced gastritis has been observed in preclinical studies, it has not been previously reported in patients. We retrospectively analyzed patients with human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2-positive, advanced gastric or gastroesophageal junction cancer who underwent endoscopy during first-line zolbetuximab-containing chemotherapy. Patients who had undergone prior total gastrectomy were excluded. We evaluated associations between gastritis and clinical outcomes including GI toxicities and serum albumin level. Among 58 eligible patients, gastritis was observed in 52 (89.7%) at a median of 7.8 weeks after treatment initiation. Characteristic endoscopic findings included mucosal erythema (100%), white exudate (63.4%), edema (28.8%), and erosions or ulcerations (26.9%). The distribution of gastritis was predominantly diffuse (76.9%) rather than scattered (23.1%), commonly involving multiple gastric regions (90.4%). Patients with diffuse gastritis experienced significantly higher rates of any-grade anorexia compared with those without gastritis (97.5% versus 50.0%, P = 0.005) and more profound serum albumin decline [median decrease -1.2 g/dl, interquartile range (IQR) -1.525 to -0.9 g/dl versus -0.7 g/dl, IQR -0.8 to -0.6 g/dl; P = 0.012]. No patients discontinued treatment due to gastritis. Among 32 patients who underwent follow-up endoscopy during ongoing treatment, improvement was confirmed in 25 patients, and no cases exhibited unresolved gastritis beyond 18 weeks. Early-onset transient gastritis frequently occurred following zolbetuximab-containing therapy and was significantly associated with anorexia and hypoalbuminemia. A deeper understanding of gastritis underlying unique GI toxicities may provide insight into effective management.