This protocol addresses patients with radioiodine-refractory (RAIR), progressive papillary thyroid carcinoma in whom biomarker testing has excluded actionable oncogenic driver alterations, and whose disease has progressed on or following first-line multikinase inhibitor therapy.
The patient has RAIR progressive papillary thyroid carcinoma and has undergone tissue-based biomarker testing confirming the absence of actionable oncogenic drivers — specifically no NTRK fusion, no RET fusion, no BRAF V600E mutation, and no ALK fusion. This rules out targeted therapies linked to those alterations and places the patient in the MKI-eligible pathway.
First-line therapy in this setting — lenvatinib (the preferred first-line multikinase inhibitor) or sorafenib as an alternative — has not achieved adequate disease control. Escalation to this protocol is triggered when target lesion diameters increase by 20% or more, or when new metastatic foci appear. The goal of sustained disease stability was not reached, and a next treatment step is required.
For patients who desire continued treatment and have no contraindication, a specific oral targeted agent is indicated as second-line therapy. The complete regimen, eligibility criteria, and clinical management details are available in the structured protocol.
Tissue-based biomarker testing to identify actionable oncogenic driver alterations in RAIR DTC should be performed prior to initiating systemic therapy for progressive disease.
For patients with progressive RAIR DTC without an actionable biomarker-linked FDA-approved first-line therapy, MKI therapy with either lenvatinib or sorafenib is recommended.
Cabozantinib should be offered as second-line therapy for patients with RAIR DTC without an actionable oncogenic driver alteration who have progressed on or did not tolerate, prior MKI therapy, if they desire ongoing treatment, and do not have a contraindication to therapy.
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