Anti emetic efficacy of Low dose Olanzapine non-Inferior to high dose in patients with Solid tumors

The study evaluated the effectiveness of giving patients with solid tumors a low dose of olanzapine compared to the standard dose after undergoing highly emetogenic chemotherapy.

This study was conducted at Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India. Patients aged 13–75 years with an Eastern Cooperative Oncology Group performance status of 0–2 who received doxorubicin–cyclophosphamide or high-dose cisplatin for a solid tumour were eligible.

Patients were randomly assigned to receive either low-dose (2.5 mg) or standard-dose (10.0 mg) oral olanzapine, with block randomization and stratification based on sex, age, and chemotherapy regimen. The study's primary endpoint was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea, assessed in the modified intention-to-treat population. Daytime somnolence was the safety endpoint of interest, and non-inferiority was shown if the upper limit of the one-sided 95% CI for the difference in the complete control proportions excluded the non-inferiority margin of 10.

Key findings from the study are:

· Between February 9, 2021, and May 30, 2023, 356 patients were pre-screened for eligibility.

· 275 were enrolled and randomly assigned to two groups: 134 patients received 2.5 mg of olanzapine, and 141 received 10.0 mg of olanzapine.

· 267 patients (132 in the 2·5 mg group and 135 in the 10·0 mg group) were included in the mITT population, with 94% being female, 6% male, and 91% having breast cancer.

· 59/132 patients in the 2·5 mg olanzapine group had complete control in the overall phase versus 59/135 in the 10·0 mg olanzapine group. The difference was –1·0%.

· In the overall phase, there were significantly fewer patients in the 2·5 mg olanzapine group than in the 10·0 mg olanzapine group with daytime somnolence of any grade (86/ 132 vs 121/135; p<0·0001) and of severe grade on day 1.

They further interpreted that our study indicates that olanzapine 2.5 mg is comparable to 10.0 mg in preventing nausea and vomiting and causes less daytime somnolence in patients undergoing highly emetic chemotherapy, making it a potential new standard of care.

They added that the low-dose regimen successfully managed emetic episodes without using rescue medications and significantly decreased daytime drowsiness.

The Progressive Ladies Welfare Association funded the study.

Reference:

Bajpai 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, randomized, controlled, phase 3 trial. The Lancet Oncology. January 12, 2024DOI:https://doi.org/10.1016/S1470-2045(23)00628-9