Olanzapine for Managing Side Effects From Antiangiogenic Tyrosine-Kinase Inhibitors.

Context: Side effects from tyrosine kinase inhibitors (TKIs) are common and burdensome. Olanzapine is useful for managing symptoms from conventional chemotherapy, but its role in treating TKI-related side effects is unclear.

Objectives: Examine the efficacy of olanzapine for TKI-induced nausea, vomiting, anorexia, weight loss, and insomnia.

Methods: All patients prescribed olanzapine with lenvatinib, cabozantinib, axitinib, or tivozanib at Mayo Clinic between January 2018 and June 2024 were assessed for inclusion. For baseline assessment, clinical notes documenting symptoms and indication(s) for starting olanzapine were reviewed. Notes and portal messages from the first three months after starting olanzapine were then evaluated for qualitative descriptions of change in symptom burden. Data were categorized as "improved," "worsened," "stable," or "missing data," with each symptom domain analyzed independently, when olanzapine was prescribed for multiple interrelated symptoms.

Results: Sixty patients received olanzapine, most commonly 5 mg (n = 37, 61.7%) or 2.5 mg (n = 16, 26.6%). Indications included nausea without vomiting (n = 35), anorexia (n = 25), nausea with vomiting (n = 16), weight loss (n = 16), and insomnia (n = 11). It was given for multiple symptoms in 32 patients. Within the first 3 months, 85% of patients had improvement in nausea without vomiting, 93% in nausea with vomiting, 74% in appetite, and 85% in sleep. Among 34 patients with weight loss prior to olanzapine, 50% gained weight (median: 6.1 kg), 26% stabilized (±1 kg), and 24% continued to lose weight. Only 4 patients discontinued olanzapine due to side effects.

Conclusion: Olanzapine appears effective in treating TKI-induced nausea, vomiting, anorexia, insomnia, and weight loss, warranting further investigation in prospective studies.