What antiemetics were recommended or used in zolbetuximab trials?

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Prescribing Information including BOXED WARNING

NK-1 and 5-HT₃ receptor antagonists, plus other prophylactic antiemetics, were recommended and given prior to the first zolbetuximab infusion in Phase 3 trials.

The SPOTLIGHT and GLOW clinical trial protocols recommended the use of NK-1 and 5-HT₃ receptor antagonists, as well as other prophylactic antiemetics, per institutional standards of care and published guidelines, before zolbetuximab/placebo infusions.^1,2

Intravenous antiemetic premedication was recommended prior to zolbetuximab/placebo infusion while oral premedication was suggested ≥ 30 minutes before each study treatment.

Combined ad hoc exploratory analyses examined prophylactic antiemetic regimens used and incidence rates of nausea/vomiting on Cycle 1, Day 1 in SPOTLIGHT and GLOW.³ Various combinations of antiemetics were administered before zolbetuximab/placebo infusions.

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.

Table 1. Use of prophylactic antiemetics and occurrence of nausea or vomiting on the day of the first zolbetuximab infusion^a^,³

Use of prophylactic antiemetics, n (%)	n	With nausea	Without nausea	With vomiting	Without vomiting
Any antiemetics
Yes	521	242	279	213	308
No	8	4	4	4	4
Standard antiemetic regimens^b	377	174 (46.2)	203 (53.8)	139 (36.9)	238 (63.1)
2-drug antiemetic regimens
NK-1 receptor antagonist + 5-HT₃ receptor antagonist	187	94 (50.3)	93 (49.7)	70 (37.4)	117 (62.6)
5-HT₃ receptor antagonist + steroid	93	42 (45.2)	51 (54.8)	45 (48.4)	48 (51.6)
3-drug antiemetic regimens
NK-1 receptor antagonist+ 5-HT₃ receptor antagonist + steroid	97	38 (39.2)	59 (60.8)	24 (24.7)	73 (75.3)
Other antiemetic regimens^c	144	68 (47.2)	76 (52.8)	74 (51.4)	70 (48.6)

^aData represent the combined analysis of SPOTLIGHT and GLOW.

^bGiven that sample sizes beyond three-drug antiemetic regimens were small, various combinations of antiemetics not commonly used may not have been captured. Antiemetic regimens were excluded if not accurately documented as prophylactic or concomitant medication.

^cIncludes patients with less-common combinations of antiemetics as prophylactic or concomitant medications.

Table 2. Use of prophylactic antiemetics and the occurrence of nausea or vomiting on the day of the first placebo infusion^a^,³

Use of prophylactic antiemetics, n (%)	n	With nausea	Without nausea	With vomiting	Without vomiting
Any antiemetics
Yes	522	62	460	16	506
No	4	0	4	0	4
Standard antiemetic regimens^b	375	48 (12.8)	327 (87.2)	9 (2.4)	366 (97.6)
2-drug antiemetic regimens
NK-1 receptor antagonist + 5-HT₃ receptor antagonist	201	35 (17.4)	166 (82.6)	8 (4.0)	193 (96.0)
5-HT₃ receptor antagonist + steroid	89	6 (6.7)	83 (93.3)	1 (1.1)	88 (98.9)
3-drug antiemetic regimens
NK-1 receptor antagonist+ 5-HT₃ receptor antagonist + steroid	85	7 (8.2)	78 (91.8)	0	85 (100.0)
Other antiemetic regimens^c	147	14 (9.5)	133 (90.5)	7 (4.8)	140 (95.2)

^aData represent the combined analysis of SPOTLIGHT and GLOW.

^cIncludes patients with uncommon combinations of antiemetics as prophylactic or concomitant medications.

The prophylactic antiemetics given to ≥ 5% of patients may be accessed using the link below:⁴

Prophylactic antiemetics ≥ 5%

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.
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.
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.
Data on File.