Slower Infusion of Antiemetic Drugs May Help With Nausea in GI Cancers

Slower infusion rates of antiemetic combination drugs have been shown to manage side effects of nausea and vomiting in patients with claudin-18.2-positive, HER2-negative, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, according to results of two phase 3 trials.

Researchers found that implementing slower infusion rates of antiemetic combination drugs for nausea and vomiting would allow patients to receive a maximum clinical benefit of zolbetuximab plus chemotherapy.

Findings regarding the management of nausea and vomiting in this patient population were presented at the 2024 Gastrointestinal Cancers Symposium and discussed in an interview with Dr. Kohei Shitara, who was the lead study author, as well as a medical oncologist and chief of the Department of Gastrointestinal Oncology of the National Cancer Center Hospital East in Kashiwa, Japan.

The two trials included the SPOTLIGHT and GLOW trials. In the SPOTLIGHT trial, 565 patients either received zolbetuximab plus a chemotherapy regimen or placebo plus the chemotherapy regimen. The GLOW trial included 507 patients, in which patients either received zolbetuximab plus a different chemotherapy regimen or placebo plus the respective chemotherapy regimen.

Both trials recommended neurokinin-1 receptor blockers (NK-1 inhibitors), selective serotonin receptor blockers (5-HT3 inhibitors) and other prophylactic antiemetic regimens to help prevent or manage nausea and vomiting in patients.

Transcript:

So in this ASCO GI meeting, we also presented the subgroup … analysis from phase 3 of zolbetuximab of the claudin-18.2 targeted therapy for claudin-positive gastric (or gastroesophageal junction) cancer, especially the toxicity profile.

Claudin is expressing in gastric and normal tissues, so that is a reason for toxicity, or like nausea and vomiting. Actually, 50% to 60% of patients experienced all-grade nausea in previous phase 3 trials, so we tried to figure out the characteristics and timing and … efficacy of antiemetics during the study.

We evaluated the timing of recurrence and the nausea and vomiting after infusion of zolbetuximab. Median time to onset is around one hour, so that means always this kind of toxicity occurred during the infusion. And then we try to compare the patient if we require dose interruption by toxicity. And the patients who can complete the treatment without interruption and there is a trend that patients (who) require dose interruption receive a higher rate or faster infusion at the beginning. And patients who don't have such experience received a slower infusion. So that suggests that a lower and slower infusion may somehow be helpful to reduce the GI toxicity.

We also tried to compare that such kind of incidence of nausea and vomiting by antiemetics. Actually, 90% of patients received a 5-HT3 inhibitor, half of patients received an NK-1 inhibitor and 40% of patients also received a steroid. And there is no clear trend. But there's some trend to show (that) there's a lower incidence of vomiting in patients receiving … a combination of antiemetics, including the 5-HT3 and NK-1 as well as a steroid. So this may be somehow helpful.

Finally, we also compared the survival outcome or efficacy outcome according to the use of steroids, because at the beginning of this study, there was some preclinical concern that the steroid may affect the activity of zolbetuximab. So in the protocol, steroid is not recommended, but not completely prohibited. So that's why 40% of patients receiving steroids (had) no negative impact, because patients who received the corticosteroids as prophylaxis also achieved the same degree of magnitude of PFS (progression-free survival) and OS (overall survival) benefit. So in summary, kind of nausea and vomiting occurred earlier in the other phase during the infusion, especially at the first cycle and slower infusion at the beginning and the use of antiemetics may somehow be helpful to reduce such GI toxicity and the use of a steroid seem to have no negative impact of efficacy. So I hope this kind of information is helpful for the clinical use of zolbetuximab after its approval.

Transcript was edited for clarity and conciseness.

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