About 85% of thyroid malignancies are differentiated thyroid carcinoma (DTC), of which 15% develop distant metastasis requiring radioactive iodine (RAI), and about half become RAI-refractory. Radioiodine-refractory differentiated thyroid carcinoma (RRDTC) is an independent entity requiring multikinase inhibitors (MKIs) to improve survival. Lenvatinib is the first-line MKI with favorable outcomes in trials of selected populations. We retrospectively reviewed medical records to identify factors associated with lenvatinib response in real-world experiences.

In a medical center of southern Taiwan, we screened subjects from the database of the pre-review system applying for lenvatinib regulated by National Health insurance. Totally 90 patients fulfilled the diagnostic criteria of RRDTC from Oct 2016 to Dec 2024. Three patients with concurrent active malignancies under treatment, four intolerant to lenvatinib, nine treated or followed for less than six months, and eleven never received lenvatinib were excluded. Finally, 63 patients remained, divided into 54 responders and 9 non-responders to lenvatinib according to radiological diagnosis. We compared 25 factors based on literature review and available data between the two groups.

Among the 25 factors, significantly lower cumulative radioiodine dosage before lenvatinib started (359mCi vs. 550mCi, p=0.016), more lung metastasis (92.3% vs 54.5%, p=0.006), and less bone metastasis (66.7% vs. 91.7%, p=0.029) were observed in the responders, with borderline significance of more female patients (94.1% vs. 75.9%, p=0.068) and less metastases to locations besides lymph node, lung, bone, and brain (33.3% vs. 88.3%, p=0.051). No statistical differences were found in age at diagnosis, age when lenvatinib started, levothyroxine maintenance dosage, FT4, TSH, serum thyroglobulin and thyroglobulin antibody levels at the time of lenvatinib initiation, clinical stage, histological subtype, confirmation of radio-refractory lesions by scintigraphy, and the presence of genetic mutations. Furthermore, occurrence of lenvatinib-related adverse effects were not predictive of treatment response in our cohort.

This was the first report in Taiwan regarding the lenvatinib-responsive factors in RRDTC. Our results were consistent with previous reports, confirming more lung and less bone metastases in lenvatinib responders. Surprisingly, we also observed a lower cumulative radioiodine dosage before starting lenvatinib in the responders, a factor less emphasized in prior studies, indicating earlier initiation of lenvatinib might be beneficial. These findings highlighted potentially useful predictors for pretreatment evaluation and individualized therapeutic planning in patients with RRDTC receiving lenvatinib.