How was zolbetuximab dose adjusted for nausea in SPOTLIGHT/GLOW?

Published

Continue zolbetuximab for Grade 1-2 nausea; interrupt and restart at a lower rate for Grade 3; treat per local standard of care for Grade 4

Guidance for Grade 3 nausea:1,2

  • Interrupt infusion.
  • Pause zolbetuximab treatment until toxicity has improved to Grade ≤ 1, then restart the infusion at a lower rate.
  • If the investigator determines that the toxicity is not related to zolbetuximab and the toxicity has improved to Grade ≤ 2, then infusion may be restarted at the investigator’s discretion at a lower rate.

Per the SPOTLIGHT and GLOW protocols, adverse events were graded for severity according to the National Cancer Institute-Common Terminology Criteria For Adverse Events (NCICTCAE) v4.03.1,2

Consensus guidance3

An international RAND/UCLA Modified Delphi Panel was formed to determine consensus guidance for preventing and managing nausea and vomiting associated with zolbetuximab + chemotherapy. A complete overview, including key recommendations on infusion rate modifications for managing nausea and vomiting according to the Modified Delphi Consensus guidance, can be accessed using the link below:

Real-world evidence4–6

Three single-institute observational studies evaluated various protocols for managing zolbetuximabinduced nausea and vomiting in patients with advanced gastric cancer, including information on zolbetuximab administration. An overview of these studies can be accessed using the link below:

  1. Shitara K, Lordick F, Bang YJ, et al. Supplement to: 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.

  2. Shah MA, Shitara K, Ajani JA, et al. Supplement to: 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.

  3. 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;7:100131. Available at: https://doi.org/10.1016/j.esmogo.2024.100131.

  4. 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;7:100128. Available at: https://doi.org/10.1016/j.esmogo.2024.100128.

  5. 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.

  6. 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.

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