Managing zolbetuximab-induced nausea and vomiting: a proposal for a pragmatic approach in clinical practice

Background: The global phase III SPOTLIGHT and GLOW trials confirmed the superiority of zolbetuximab plus chemotherapy over chemotherapy alone for claudin 18.2-positive advanced gastric cancer (AGC). However, severe nausea/vomiting during zolbetuximab infusion remains a significant safety concern. Our study aimed to evaluate the safety management strategy’s applicability in our institution. Patients and methods: This registry-based observational study assessed the combination of fosnetupitant, dexamethasone, and 5-HT3-receptor antagonist in patients receiving zolbetuximab plus chemotherapy. The initial zolbetuximab infusion rate was set at 75 ml/h for the first 60 min, and then 250 ml/h thereafter. The primary endpoint was the feasibility of our management and vomiting prevention during cycle 1. Results: Among 21 patients (median age 61 years; male 48%; diffuse-type histology 81%; prior gastrectomy 38%; peritoneal metastases 57%), the incidence of nausea/vomiting during zolbetuximab initiation in cycle 1 was 62%/9.5%, with a 62% infusion interruption rate. The median time to first nausea was 93 min (range 77-127 min); median interruption time was 40 min (16-68 min); and median total infusion time of zolbetuximab was 257 min (154-343 min). All patients successfully completed zolbetuximab administration in cycle 1, with an 81% vomiting prevention rate. At cycle 2 day 1, 3 of 14 patients (21%) experienced nausea, with no vomiting. Conclusion: First-line zolbetuximab plus chemotherapy was safely introduced to real-world patients with claudin 18.2-positive AGC, with effective management of nausea and vomiting, applicable in clinical practice.