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Purpose <p>Tropomyosin receptor kinase (TRK) inhibitors have emerged as a promising class of targeted therapies for patients with tumors containing neurotrophic tyrosine receptor kinase (<i>NTRK</i>) 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.</p> Case presentation <p>A 35-year old male with metastatic/recurrent <i>ETV6-NTRK3</i> 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&#xa0;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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年10月22日

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  • Reema Patel,
  • John F. Deeken

摘要

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.