TARGETED THERAPIES VS. STANDARD TYROSINE KINASE INHIBITORS IN ADVANCED THYROID CANCER: A COMPARATIVE REVIEW OF UPDATED FDA APPROVALS AND NCCN GUIDELINES

Background: Advanced thyroid cancer, including radioiodine-refractory differentiated thyroid cancer (RR-DTC), medullary thyroid cancer (MTC), and anaplastic thyroid cancer (ATC), has historically been associated with poor outcomes due to limited treatment options. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized the systemic therapy landscape for these aggressive malignancies. Objective: This narrative review aims to compare the efficacy, safety, and clinical utility of standard multikinase inhibitors (MKIs) with newer, highly selective targeted therapies in the management of advanced thyroid cancer. It provides a critical synthesis of updated FDA approvals and the latest NCCN Clinical Practice Guidelines. Methods: A comprehensive literature search was conducted in PubMed, focusing on peer-reviewed articles, clinical trials, and systematic reviews published between 2020 and 2025. Key search terms included “advanced thyroid cancer,” “targeted therapy,” “tyrosine kinase inhibitors,” “FDA approval,” and “NCCN guidelines.” Key Findings: The review confirms that MKIs like lenvatinib and sorafenib remain the standard first-line therapy for RR-DTC due to robust progression-free survival (PFS) benefits, albeit with significant toxicity. However, the treatment paradigm is shifting toward precision medicine. Highly selective inhibitors targeting specific driver mutations—such as selpercatinib and pralsetinib for RET-altered tumors, dabrafenib/trametinib for BRAF V600E-mutant ATC, and larotrectinib for NTRK fusions—demonstrate superior response rates and more favorable tolerability profiles. Consequently, NCCN guidelines have increasingly prioritized these biomarker-driven therapies. Conclusion: While standard MKIs continue to play a crucial role, the future of advanced thyroid cancer treatment lies in highly selective targeted therapies guided by comprehensive molecular profiling. This shift promises improved clinical outcomes and quality of life, though challenges such as acquired resistance and equitable access to molecular testing and novel agents remain.

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