Incretin Receptor Agonist, Semaglutide, as a Treatment for Alectinib-Induced Excessive Weight Gain. A Case Report

Alectinib is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that has been widely used as first-line (1L) treatment of advanced ALK+ non-small cell lung cancer (NSCLC) ever since its approved indication on November 17, 2017, based on the ALEX trial and its perceived well-tolerability. Lorlatinib, a third-generation ALK TKI, achieved 1L indication on March 3, 2021, but is generally associated with adverse events including weight gain in up to 44% of patients from the recent update of the CROWN study; hence its use as 1L treatment has lagged behind alectinib. Recently, alectinib has also been reported to cause significant weight gain. Incretin receptor agonists such as glucagon-like peptide-1 receptor (GLP-1) agonists semaglutide have been approved to treat obesity (body mass index [BMI] ≥ 30). Here, we report a patient's case who had gained significant weight during still on-going 12-year treatment with alectinib and achieved weight loss through semaglutide but discontinued several months after starting semaglutide due to acute gallstone pancreatitis requiring emergency cholecystectomy. We believe this is the first case report on the efficacy and potential adverse events of GLP-1 agonist in treating the weight gain induced by alectinib.