What antiemetics are recommended with zolbetuximab

Modified Delphi Panel Consensus Guidance¹ 

It may be necessary to escalate the antiemetic regimen in the second and subsequent infusions.

• If a patient has experienced only nausea (no vomiting) with the previous zolbetuximab infusion, with the next infusion, either: make no change to the previous antiemetic regimen or escalate the antiemetic regimen from the previous infusion.
• If a patient has experienced vomiting with the previous zolbetuximab infusion, with the next infusion, escalate the antiemetic regimen from the previous infusion.

Zolbetuximab should not be discontinued permanently without first attempting to modify or temporarily interrupt the infusion and/or without providing additional treatment for nausea and vomiting in the absence of hypersensitivity reactions or infusion-related reactions.

A complete overview of the Consensus Guidance can be accessed using the link below.

• The Modified Delphi Panel Consensus Guidance

Phase 3 clinical trials: SPOTLIGHT and GLOW^3,4

Ad hoc exploratory analyses examined prophylactic antiemetic regimens used and incidence rates of nausea/vomiting on Cycle 1, Day 1 in SPOTLIGHT and GLOW.²

• Various combinations of antiemetics were given prophylactically prior to the first zolbetuximab infusion. 
• Using a 3-drug prophylactic antiemetic regimen before zolbetuximab, 75.3% (73/97) of patients did not experience vomiting, and 60.8% (59/97) of patients did not experience nausea.
• Using a 2-drug prophylactic antiemetic regimen before zolbetuximab, 58.9% (165/280) of patients did not experience vomiting and 51.4% (144/280) did not experience nausea.
• Patients who received steroids as part of a 2- or 3-drug antiemetic regimen had lower rates of nausea and vomiting, and an ad hoc analysis found that patients treated with zolbetuximab + steroids had numerically higher PFS and OS compared to those who received zolbetuximab without steroids.

Additional information can be accessed using the link below.

• Antiemetic recommendations and usage in the zolbetuximab Phase 3 trials

Real-world evidence

Three real-world studies describe protocols for managing nausea and vomiting with prophylactic antiemetics.

• Shimozaki et al. developed a protocol for managing zolbetuximab-induced gastrointestinal toxicity and included administration of mandatory NK-1 receptor antagonist, H1 antagonist, H2 antagonist, 5-HT3 receptor antagonist, dexamethasone, and optional olanzapine given over three to five days.⁵
• The protocol developed by Narita et al. for zolbetuximab-induced gastrointestinal toxicity included mandatory NK-1 receptor antagonist, 5-HT3 receptor antagonist, dexamethasone, chlorpheniramine, vonoprazan, rebamipide and optional olanzapine administered over six days.⁶
• Yakuwa et al.’s protocol for zolbetuximab administration included premedication given over two to four days with oral diphenhydramine hydrochloride and olanzapine and intravenous fosnetupitant, palonosetron, and dexamethasone. In patients with severe anxiety, alprazolam or lorazepam was optional.⁷

Brief summaries of these studies can be accessed using the link below.

• Real-world evidence on incidence and management of nausea and vomiting

1. Klempner SJ, Pazo-Cid RA, Lonardi S, et al. Consensus guidance for prevention and management of nausea and vomiting in patients treated with zolbetuximab + chemotherapy: a RAND/UCLA modified Delphi panel study. ESMO Gastrointest. Oncol. 2025;7100131. Available at: https://doi.org/10.1016/j.esmogo.2024.100131.
2. Shitara K, Smith E, Lordick F, et al. Impact and effective management of nausea/vomiting on patients treated with zolbetuximab + chemotherapy: insights from the phase III SPOTLIGHT and GLOW studies. ESMO Open. 2026;epub ahead of print105931. Available at: https://doi.org/10.1016/j.esmoop.2025.105931.
3. Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401(10389):1655-1668. Available at: https://doi.org/10.1016/s0140-6736(23)00620-7.
4. Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat. Med. 2023;29(8):2133-2141. Available at: https://doi.org/10.1038/s41591-023-02465-7.
5. Shimozaki K, Ooki A, Yamahata Y, et al. Managing zolbetuximab-induced nausea and vomiting: a proposal for a pragmatic approach in clinical practice. ESMO Gastrointest. Oncol. 2025;7100128. Available at: https://doi.org/10.1016/j.esmogo.2024.100128.
6. Narita Y, Mizuno T, Suda T, et al. Practical Management of Zolbetuximab Administration: The Project VYLOY Initiative. Cancers. 2025;17(12):1996. Available at: https://doi.org/10.3390/cancers17121996.
7. Yakuwa E, Shoji Y, Oizumi T, et al. Safety and Feasibility of Outpatient Zolbetuximab Administration in Community Cancer Care: A Mixed-methods Analysis. Vivo. 2025;39(2):951-960. Available at: https://doi.org/10.21873/invivo.13900.