Lower-Dose Olanzapine Noninferior to Standard Dose to Control Nausea/Vomiting in Patients With Solid Tumors Receiving Chemo

Lower-Dose Olanzapine Noninferior to Standard Dose to Control Nausea/Vomiting in Patients With Solid Tumors Receiving Chemo

A 2.5-mg dose of olanzapine may be noninferior to a 10.0-mg dose of the drug to prevent nausea and vomiting in patients with solid tumors who are being treated with highly emetogenic chemotherapy, recent study findings demonstrated.

“Our findings suggest that olanzapine 2.5 mg is noninferior to 10.0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy, and should be considered as a new standard of care,” the researchers wrote in the study published in The Lancet Oncology.

Complete control of emetic episodes was achieved in 59 of 132 patients (45%) assigned 2.5 mg of olanzapine for up to 120 hours compared with 59 of 135 patients (44%) assigned the 10.0-mg dose (difference, –1.0%; 1-sided 95% CI, –100.0% to 9.0%; P = .87). Significantly fewer patients experienced daytime somnolence of any grade in the 2.5-mg group compared with the 10.0-mg group (65% vs 90%; P < .0001). The lower-dose group also had significantly fewer patients experience severe grade somnolence at day 1 (5% vs 40%; P < .0001).

Although olanzapine is known to be an effective antiemetic agent, it may result in substantial daytime drowsiness or a desire to fall asleep (also known as somnolence) when given to patients at the standard dose. Researchers conducting this study aimed to compare a low dose with a high dose in patients with solid tumors after receiving highly emetogenic chemotherapy.

In this single-center, open-label, noninferiority, randomized-controlled phase 3 trial, researchers enrolled patients aged 13 to 75 years. These patients had an Eastern Cooperative Oncology Group performance status between 0 and 2, and were being treated with high-dose cisplatin or doxorubicin-cyclophosphamide for a solid tumor.

Patients in this study were randomized 1:1 to receive low-dose oral olanzapine, which consisted of 2.5 mg of the drug, or a standard dose, which was 10.0 mg. Of note, patients were randomized with block randomization (block sizes of 2 or 4) and stratified by age (older or younger than 55 years), sex, and chemotherapy regimen. The assigned regimen was given to patients for 4 days with a triple antiemetic regimen. Although study staff were masked to the treatment patients were receiving, the patients, themselves knew which group they were assigned to.

The primary end point was complete control, defined as no rescue medications, no emetic episodes, and either no or mild nausea in the overall phase (0-120 hours). This specific end point was assessed in the modified intention-to-treat population, which included all patients who received protocol-specified treatment and excluded patients who withdrew consent from the study after randomization or those with eligibility violations. The safety end point of interest for this study was daytime somnolence.

Researchers determined that noninferiority would be shown if the upper limit of the 1-sided 95% CI for the difference in complete control populations in both groups excluded the noninferiority margin of 10%.

Between Feb. 9, 2021, and May 30, 2023, researchers prescreened 356 patients for eligibility, of whom 275 patients were enrolled into the study. Within these patients, 134 were assigned to the 2.5-mg dose of olanzapine and 141 were assigned to the 10.0-mg dose. In addition, 267 patients were included in the modified intention-to-treat population, consisting of 132 patients from the 2.5-mg group and 135 from the 10.0-mg group. In the modified intention-to-treat group, 252 (94%) were female, and 242 patients (91%) had breast cancer.

Reference

Bajpai J, Kapu V, Rath S, et al. Low-dose versus standard-dose olanzapine with triple antiemetic therapy for prevention of highly emetogenic chemotherapy-induced nausea and vomiting in patients with solid tumours: a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial. Lancet Oncol. 2024;25(2):246-254. doi:10.1016/S1470-2045(23)00628-9