ASCO recently released a new rapid recommendation update that addresses the use of olanzapine to treat cancer-related cachexia, a topic originally addressed in its 2020 guideline on the management of cancer cachexia in adults with advanced cancer.1,2 At that time, there was insufficient evidence to strongly endorse any pharmacologic agent, including olanzapine, for patients with cancer experiencing loss of weight or appetite.
“At the time, things looked promising [for olanzapine], but we didn’t have any high-quality data,” said Eric J. Roeland, MD, of Oregon Health & Science University Knight Cancer Institute, and Guideline Co-Chair.
Eric J. Roeland, MD
Available data at that time were from a 2010 study comparing olanzapine plus megestrol acetate with megestrol acetate alone in 80 patients with advanced gastrointestinal or lung cancer. The addition of olanzapine to megestrol acetate yielded significantly more weight gain than megestrol acetate alone and had a pronounced effect on appetite.3
“The data were not from a placebo-controlled trial though, and with symptom interventions, it is important to have data from a placebo-controlled trial, because the placebo effect can be as high as 30% in some studies,” Dr. Roeland said.
The rapid recommendation update was prompted by the Journal of Clinical Oncology publication of a placebo-controlled trial from researchers in India. Lakshmi Sandhya, MD, of Jawaharlal Institute of Postgraduate Medical Education & Research, in Puducherry, India, and colleagues enrolled 124 patients with untreated, locally advanced, or metastatic cancers. They randomly assigned them to receive 2.5 mg of olanzapine or placebo once a day for 12 weeks along with cytotoxic chemotherapy.4
“There was substantial benefit for olanzapine in terms of improved appetite, decreased toxicities, and weight gain,” said Charles L. Loprinzi, MD, of Mayo Clinic in Rochester, Minnesota, and Guideline Co-Chair.
Charles L. Loprinzi, MD
A greater proportion of patients assigned to olanzapine had weight gain of greater than 5% (60% vs 9%; P < .001). Improvement in appetite was greater with olanzapine compared with placebo, as measured by a visual analog scale (43% vs 13%; P < .001). There also was an improvement by the Functional Assessment of Chronic Illness Therapy system of Quality-of-Life questionnaires Anorexia Cachexia subscale (22% vs 4%; P = .004).
“We now have convincing evidence that olanzapine is helpful for treating cancer anorexia/cachexia,” Dr. Loprinzi said. Dr. Roeland agreed, calling these data “practice-changing.”
Based on these data, the new update included two recommendations: First, it is recommended that clinicians now offer low-dose olanzapine once daily to improve weight gain and appetite. This recommendation was published with a qualifying statement that the majority of evidence on which this recommendation is based involved patients with lung or gastrointestinal cancer, and that in the newest and largest trial, patients were receiving cytotoxic chemotherapy. Second, for patients who cannot tolerate low-dose olanzapine, clinicians may offer a short-term trial of a progesterone analog or a corticosteroid to those experiencing loss of weight and/or appetite.
Overall, olanzapine was found to be a well-tolerated drug, Dr. Loprinzi said. The drug may cause drowsiness when it is initiated, so patients may want to take it in the evening and avoid driving while adjusting to the medication, he added.
This additional evidence on the benefit of olanzapine for cancer anorexia/cachexia also gives clinicians and researchers additional questions to answer, Dr. Roeland said. First, will there be the same impact on appetite/weight gain in a population of patients in the United States and Europe with this low dose of olanzapine? Second, what will the best dose be?
“Another huge unmet need will be understanding how olanzapine impacts people with hematologic malignancies,” Dr. Roeland said, “because they too have a huge unmet need to address appetite loss.”
1. Roeland EJ, Bohlke K, Baracos VE, et al: Management of cancer cachexia: ASCO guideline. J Clin Oncol 38:2438-2453, 2020.
3. Navari RM, Brenner MC: Treatment of cancer-related anorexia with olanzapine and megestrol acetate: A randomized trial. Support Care Cancer 18:951-956, 2010.
4. Sandhya L, Sreenivasan ND, Goenka L, et al: Randomized double-blind placebo-controlled study of olanzapine for chemotherapy-related anorexia in patients with locally advanced or metastatic gastric, hepatopancreaticobiliary, and lung cancer. J Clin Oncol 41:2617-2627, 2023.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, August 9, 2023. All rights reserved.