ABSTRACT
Anaplastic thyroid cancer is a rare but extremely aggressive type of thyroid cancer. Treatment typically consists of surgery, external beam radiotherapy and cytotoxic chemotherapy. However, available literature suggests only modest survival benefit for cytotoxic chemotherapy. Recent advances have suggested the combination of BRAF and MEK inhibition may have a profound and durable effect on patients with BRAFV600E-mutated anaplastic thyroid cancer, with a response rate of 69%. Other systemic treatments, including immunotherapies, have also shown promising but more limited results. Many clinical trials assessing the efficacy of kinase inhibitors and immunotherapies are currently ongoing.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Biomarkers, Tumor/antagonists & inhibitors , Protein Kinase Inhibitors/therapeutic use , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Neoplasms/drug therapy , Animals , Antineoplastic Agents, Immunological/adverse effects , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Biomarkers, Tumor/metabolism , Drug Resistance, Neoplasm , Genetic Predisposition to Disease , Humans , Molecular Targeted Therapy , Phenotype , Protein Kinase Inhibitors/adverse effects , Signal Transduction/drug effects , Thyroid Carcinoma, Anaplastic/enzymology , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Carcinoma, Anaplastic/immunology , Thyroid Neoplasms/enzymology , Thyroid Neoplasms/genetics , Thyroid Neoplasms/immunology , Treatment OutcomeABSTRACT
Curative therapies for radioiodine-refractory differentiated thyroid cancer remain lacking. However, oral multikinase inhibitors often allow for disease control and improved progression-free survival. Two agents, lenvatinib and sorafenib, have been approved for radioiodine-refractory differentiated thyroid cancer on the basis of phase III clinical trials showing marked response rates and improved progression-free survival over placebo. Several other multikinase inhibitors, including apatinib, axitinib, cabozantinib, pazopanib, sunitinib and vandetanib, have also been studied in phase II clinical trials, with varying response rates and comparable progression-free survival. Selective kinase inhibitors, including dabrafenib, vemurafenib, selumetinib and gefitinib, offer a more targeted approach and have also been studied in phase II clinical trials. While the emergence of these treatments has changed the landscape of management of advanced thyroid cancer, clinical challenges remain, and there are many areas of ongoing research.
