Incidence and clinical characteristics of zolbetuximab-induced nausea and vomiting in CLDN18.2-positive unresectable advanced or recurrent gastric cancer: a retrospective study

Zolbetuximab for CLDN18.2-positive advanced gastric cancer frequently causes chemotherapy-induced nausea and vomiting (CINV), particularly during the first infusion. Single-center studies in Japan have reported standardized infusion protocols and antiemetic strategies; however, these uniform approaches do not allow evaluation of how differences in infusion rate settings, antiemetic combinations, or patient backgrounds influence CINV. Using real-world data from multiple institutions with various clinical practices, the aim of this study was to clarify factors associated with CINV during the first zolbetuximab infusion, focusing on infusion rate, antiemetic use, and patient characteristics. This multicenter retrospective study included patients with CLDN18.2-positive unresectable or recurrent gastric cancer who received zolbetuximab between June 2024 and April 2025. Clinical characteristics, gastrectomy status, infusion parameters, antiemetic use, and CINV events during the first infusion were extracted from electronic medical records. CINV severity was assessed using CTCAE or patient-reported scales (NRS and Faces Scale), depending on institutional practice. Accordingly, CTCAE Grade ≥ 2, NRS ≥ 3, or Faces Scale ≥ 6 were defined as moderate-or-greater nausea. Patient backgrounds were summarized using descriptive statistics. Associations between CINV and age group, sex, gastrectomy status, antiemetic combinations, and infusion-rate categories were evaluated with exploratory analyses using Fisher’s exact or χ2 tests. Forty-four patients were analyzed. CINV during the first zolbetuximab infusion was more frequent in patients without gastrectomy (38.7%) than in those with gastrectomy (7.7%). Younger age was associated with increased risk, whereas sex differences were minimal. Olanzapine use reduced the incidence of moderate-or-greater nausea or any-grade vomiting (18.2% vs 32.4%). CINV typically occurred when infusion rates reached approximately 200–250 mg/h, suggesting an increased risk when rates exceeded approximately 150 mg/h. Combined risk analysis showed that gastrectomy status had a stronger influence on CINV than age or sex, and olanzapine further reduced risk among non-gastrectomized patients. Infusion-phase CINV during the first zolbetuximab infusion was associated with both patient-related and administration-related factors in real-world practice. Quantitative evaluation of infusion-rate ranges and the influence of gastric mucosal status suggest that nausea severity may be partially modifiable through optimized infusion management and risk-adapted antiemetic strategies. These exploratory findings warrant prospective validation.