Olanzapine May Address AEs From TKIs for Kidney and Other Cancers

The addition of olanzapine improved or stabilized some patients' nausea with and without vomiting, anorexia, weight loss, and insomnia associated with the use of a TKI.

Olanzapine may be effective in managing adverse effects (AEs) from tyrosine-kinase inhibitors (TKIs) including vomiting, nausea, insomnia, anorexia, and weight loss, although prospective, randomized, placebo-controlled studies are needed to confirm these results.

Findings from this retrospective study were presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Sixty patients in this study received olanzapine to treat TKI-related AEs. Of these patients, 35 received olanzapine for nausea without vomiting, followed by 25 patients for anorexia, 16 for nausea with vomiting, 16 patients for weight loss, and 11 for insomnia. In 32 patients (53%), olanzapine was prescribed to address multiple, simultaneous symptoms. The median duration of TKI therapy when treatment with olanzapine was initiated was 70 days (range, 3-581 days).

Olanzapine led to improvements in nausea without emesis (n = 32; 84%), nausea with emesis (n = 13; 93%), anorexia (n = 26; 74%), and insomnia (n = 11; 85%). Treatment led to worsening of nausea without emesis in 3 patients (8%) and of anorexia in 2 patients (6%). Olanzapine stabilized some patients with nausea without emesis (n = 1; 3%), anorexia (n = 4; 11%), and insomnia (n = 2; 15%). Of note, there were some missing data regarding nausea without emesis (n = 2; 5%), nausea with emesis (n = 1; 7%), and anorexia (n = 3; 9%).

Additionally, before receiving olanzapine, 34 patients (57%) had documented weight loss. After treatment, half of these patients (n = 17) gained weight, with a median increase of 6.1 kg (range, 2.0-10.7). Nine patients (26%) stabilized their weight (±1 kg) and 8 patients (24%) continued to lose weight.

A TKI dose reduction was utilized by clinicians within 1 week of initiating olanzapine in 5 patients (8.3%), of whom 3 were able to resume the higher TKI dose after starting olanzapine. Four patients (7%) discontinued treatment with olanzapine within 3 months from perceived side effects, according to the abstract.

Background and Methods

Although antiangiogenic TKI treatment can play a key role in managing renal cell carcinoma and other solid malignancies, they may cause some side effects requiring dose reductions or treatment holds, according to the background section of the abstract.

“Olanzapine has been useful for palliating symptoms from classical chemotherapies and advanced cancer, but its effect on TKI-related symptoms is largely unknown,” the study authors wrote. “This retrospective study aimed to estimate the efficacy of olanzapine for TKI-induced nausea, vomiting, anorexia, weight loss, and insomnia.”

In this study, researchers analyzed data from patients prescribed olanzapine with cabozantinib (Cabometyx), lenvatinib (Lenvima), tivozanib (Fotivda), or axitinib (Inlyta). These patients were treated at Mayo Clinic between January 2018 and June 2024.

Baseline symptom assessment consisted of clinical care team notes that documented the absence or presence of symptoms, in addition to indications for starting olanzapine.

Clinical notes and patient portal messages were assessed for response assessment from the first 3 months after olanzapine initiation. Researchers noted any descriptions of change in symptom burden. The research team reviewed extractions of direct quotes from notes and messages, which were then categorized as “stable,” “improved,” “worsened,” or “missing data.”

When olanzapine was prescribed for multiple interrelated symptoms, researchers analyzed each symptom domain independently.

Regarding baseline characteristics, 60% of patients were male. The median age at diagnosis for all patients in the study was 63.7 years (IQR, 25.3-88.7). More than half of patients had renal cell carcinoma (55.0%), followed by hepatocellular carcinoma (15.0%), endometrial cancer (13.3%), endocrine cancer (11.7%), and other (5%).

The most common TKI patients were treated with was lenvatinib (45.0%), followed by cabozantinib (33.3%), axitinib (18.3%), and tivozanib (3.3%). Over half of patients were not on concomitant therapy (53.3%), although 38.3% of patients were also treated with immunotherapy, and 8.3% were treated with everolimus.

Reference

Koch R, Muniz M, Peskey C, et al. Olanzapine for managing side effects from tyrosine-kinase inhibitors. J Clin Oncol. 2025;43(suppl 5):524. doi:10.1200/JCO.2025.43.5_suppl.524