Biomarker NTRK Coverage from Every Angle

Larotrectinib in RAI-Refractory Papillary Thyroid Cancer: Case Report

By: Justine Landin, PhD
Posted: Friday, August 6, 2021

Although many patients with thyroid cancer may reap a benefit from a combination treatment approach of surgery and radioactive iodine (RAI), this strategy tends to be unsuitable for those with metastatic or RAI-refractory disease. However, the NTRK inhibitor larotrectinib may be a promising treatment for patients with papillary thyroid cancer who harbor an ETV6-NTRK3 gene fusion. In a case study published in Clinical Case Reports, a patient with progressive RAI-refractory papillary NTRK3 fusion–positive thyroid cancer achieved a complete response with larotrectinib, including intracranial responses in metastatic brain lesions.

NTRK gene fusions are an actionable alteration in differentiated thyroid cancer, and genomic profiling of RAI‐refractory differentiated thyroid cancer should be undertaken to improve the clinical course for these patients,” stated Fabián Pitoia, MD, PhD, of the University of Buenos Aires.

A 56-year-old woman presented with papillary thyroid cancer (stage IVB) and was referred to the clinic after incomplete surgical resection. RAI therapy was administered, and a whole-body scan indicated uptake solely in the thyroid bed and mediastinum, with persistent macroscopic disease and a single lung lesion larger than 15 mm. This patient was subsequently diagnosed with RAI-refractory papillary thyroid cancer. Five months following the initial referral, there were numerous metastatic sites, an uptake in multiple bones, and the lung lesion had increased to 23 mm. In addition, a metastatic lesion of the scalp was identified via biopsy.

Multiple treatments were attempted, such as zoledronic acid, sorafenib, and lenvatinib, but none reduced the rapid progression of metastases, including to the brain. Genomic sequencing using the scalp lesion indicated the presence of an ETV6-NTRK3 gene fusion. Larotrectinib was subsequently administered at a dose of 200 mg/day and was reported to be well tolerated. Following 1 month of treatment, a PET/CT scan indicated that the patient exhibited a near-complete response. By 2 months, the patient had achieved a complete response. By 7 months, all brain metastases had resolved, and elevated thyroglobulin antibody levels had returned to baseline.

Disclosure: For full disclosures of the study author, visit

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