275MO - Phase III double blind placebo-controlled study of olanzapine for chemotherapy related anorexia in patients with advanced gastric, hepatopancreaticobiliary and lung cancer

Background

Anorexia occurs in 30-80% of patients with advanced malignancies which worsens with chemotherapy. This may worsen weight loss with resultant increase in toxicity and poor oncological outcomes. There is no current standard therapy for anorexia. This trial was designed to assess the efficacy of olanzapine as an orexigenic agent in patients receiving cytotoxic chemotherapy.

Methods

Adults (≥18years) with untreated, advanced gastric, hepatopancreaticobiliary (HPB) and lung cancers were randomly assigned in a double-blind manner to receive olanzapine (2.5mg once a day for 12 weeks) or placebo along with planned chemotherapy. Both groups received standard dietary assessment and advice. Improvement in anorexia measured by “The Functional Assessment of Chronic Illness Therapy Anorexia Cachexia subscale (FAACT ACS)” and proportion of patients achieving weight gain of >5% at 12 weeks were the primary outcome measures. The study was powered to detect a 20% improvement in the proportion of patients achieving >5% weight gain in the olanzapine group.

Results

A total of 124 pts [median age: 55 yrs (18-78yrs), 64% males, mean wt: 53kgs, mean BMI: 20.9 kg/m²; Gastric (N=68,55%), lung (N=43,35%), and HPB (N=13 (10%)] were randomized, of which 58 (olanzapine) and 54 (placebo) were evaluable at 12 weeks. Proportion of patients with improvement in FAACT ACS score was superior with olanzapine [54/58 (93%) vs. 33/54(61%), p<0.0001]. Proportion achieving weight gain (≥5%) was more with olanzapine [35/58 (56%) vs. 5/54 (8%), p<0.0001] when compared to placebo. Patients on olanzapine had improvement in quality-of-life (p=0.003), SGA grade (p=0.004), and lesser grade 3 toxicity (14%vs 36%, p=0.02). No major side effects were due to olanzapine or placebo. Among patients with metastatic disease(N=99), median overall survival was better in the olanzapine arm[16 vs 10 mos (p=0.03)].

Conclusions

Low-dose olanzapine improves appetite and leads to weight gain when given along with chemotherapy with a potential to improve oncological outcomes. Olanzapine can be considered as a safe, and inexpensive addition to supportive treatment for patients receiving chemotherapy.

Clinical trial identification

CTRI/2020/08/027133.

Editorial acknowledgement

Legal entity responsible for the study

Dr. Prasanth Ganesan.

Funding

JIPMER Intramural Research Grant.

Disclosure

All authors have declared no conflicts of interest.