Olanzapine for chemotherapy-related anorexia: Impact on body composition.

12065 Background: Chemotherapy-related anorexia and weight loss are associated with adverse outcomes in patients with advanced gastrointestinal and lung cancers. While olanzapine has demonstrated efficacy in improving appetite and weight gain, the impact of weight gain on body composition remains unclear. We evaluated changes in morphomic parameters among patients receiving olanzapine during chemotherapy. Methods: In this phase III, randomized, double-blind, placebo-controlled trial, adults (≥18 years) with untreated locally advanced or metastatic gastric, hepatopancreaticobiliary, or lung cancer were randomized to receive olanzapine 2.5 mg once daily or placebo for 12 weeks, along with standard chemotherapy and nutritional counseling. The primary endpoint was the proportion of patients achieving > 5% weight gain. Secondary endpoints included changes in skeletal muscle index (SMI), subcutaneous fat index (SFI), and visceral fat index (VFI) assessed at the third lumbar vertebra on CT scans. Morphomic analysis was performed in patients with paired baseline and interim CT scans. Results: A total of 103 patients (olanzapine, n = 53; placebo, n = 50) were included in the morphomic analysis. Baseline characteristics were comparable between groups. Weight gain > 5% was significantly more frequent in the olanzapine group compared with placebo (60% vs 9%, p < 0.0001). Both groups experienced a decline in mean SMI; however, among olanzapine-treated patients with > 5% weight gain, 63% demonstrated improvement or stabilization of SMI. Improvement in SFI was more frequent with olanzapine than placebo (62% vs 40%, p = 0.047). Among patients with > 5% weight gain, a higher proportion in the olanzapine group showed an increase in VFI compared with placebo (72% vs 60%, p = 0.006). Conclusions: Olanzapine improves weight gain with favorable changes in skeletal muscle and fat indices, indicating true nutritional gain rather than fluid retention in patients with chemotherapy-related anorexia. These findings suggest that olanzapine may favorably modulate cancer-related anorexia and treatment outcomes, warranting further validation in larger focused studies. Clinical trial information: CTRI/2020/08/027133.