Larotrectinib-associated withdrawal symptoms resolved following initiation of GLP-1 receptor agonist: a case report.

PURPOSE: Tropomyosin receptor kinase (TRK) inhibitors have emerged as a promising class of targeted therapies for patients with tumors containing neurotrophic tyrosine receptor kinase (NTRK) gene fusions. While not noted in early clinical studies, about one-third of patients can experience diffuse arthralgias, myalgias, and allodynia in the contexts of missed, delayed, or discontinued therapy, resembling withdrawal-like symptoms. Here we report a case of a patient who had daily withdrawal-like symptoms which resolved after starting semaglutide. CASE PRESENTATION: A 35-year old male with metastatic/recurrent ETV6-NTRK3 fusion parotid gland cancer was enrolled on a clinical study investigating the efficacy of larotrectinib. He had a rapid complete response to therapy, and has continued on therapy for more than seven years. Early after starting therapy he experienced twice a day diffuse myalgias, arthralgias, and light sensitivity starting 30 to 45 min before his next dose was due. This continued until he was started on semaglutide, a GLP-1 receptor agonist, after which his symptoms completely resolved. CONCLUSION: GLP-1 receptor agonists may have a role in improving side effects from larotrectinib. Possible mechanisms for this effect are discussed, with further research needed.