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

Abstract

Background: 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.

Patients and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: CLDN18.2; gastric cancer; gastritis; zolbetuximab.