Comprehensive Analysis of Clinical Trials and Emerging Therapies in Thyroid Cancer

Innovative Approaches: Key Trends in Thyroid Cancer Clinical Trials

Thyroid cancer (TC), the most common type of endocrine malignancy, has evolved rapidly in that sense with respect to development of targeted therapies and immunotherapy strategies. Differentiated thyroid cancer (DTC) has been dramatically curable with traditional treatments including surgery and radioactive iodine (RAI). Novel treatment approaches such as tyrosine kinase inhibitors and combination therapies are under investigation in clinical trials for patients with advanced radioiodine-refractory or anaplastic thyroid cancer (ATC), or medullary thyroid cancer (MTC).

Tyrosine Kinase Inhibitors (TKIs) TKIs like lenvatinib, and sorafenib have emerged as main treatment modalities for RAI-refractory thyroid cancers with significant improvement in progression-free survival (PFS) in patients with advanced DTC. In anaplastic thyroid cancer (ATC) TKIs which are targeted to the BRAF mutation have shown efficacy as well, with high response rates in clinical trials in this often chemoresistant and aggressive subset of patients​

Immunotherapy is also under investigation as a promising approach, especially with respect to the aggressive subtypes. Combined trials of checkpoint inhibitors (in this case, pembrolizumab) and TKIs (like lenvatinib) have been shown to increase response rates in metastatic and refractory thyroid cancers [7​].

In addition, the success of CAR-T cell therapy in other cancers is being investigated in advanced thyroid cancer with pre-clinical work to pave way for human trials.

Combination Therapies: These is also a key trend in therapy of aggressive thyroid cancers, ie. the combination of several agents. For example, co-targeting TKIs with MEK inhibitors, mTOR inhibitors to circumvent towards resistance mechanisms. BRAF-mutant ATCs in particular have been responsive to some of these combinations such as dabrafenib/trametinib.

Patient Population and Epidemiology

Thyroid cancer (TC), the most common type of endocrine malignancy, has evolved rapidly in that sense with respect to development of targeted therapies and immunotherapy strategies. Differentiated thyroid cancer (DTC) has been dramatically curable with traditional treatments including surgery and radioactive iodine (RAI). Novel treatment approaches such as tyrosine kinase inhibitors and combination therapies are under investigation in clinical trials for patients with advanced radioiodine-refractory or anaplastic thyroid cancer (ATC), or medullary thyroid cancer (MTC).

Tyrosine Kinase Inhibitors (TKIs) TKIs like lenvatinib, and sorafenib have emerged as main treatment modalities for RAI-refractory thyroid cancers with significant improvement in progression-free survival (PFS) in patients with advanced DTC. In anaplastic thyroid cancer (ATC) TKIs which are targeted to the BRAF mutation have shown efficacy as well, with high response rates in clinical trials in this often chemoresistant and aggressive subset of patients​

Immunotherapy is also under investigation as a promising approach, especially with respect to the aggressive subtypes. Combined trials of checkpoint inhibitors (in this case, pembrolizumab) and TKIs (like lenvatinib) have been shown to increase response rates in metastatic and refractory thyroid cancers.

In addition, the success of CAR-T cell therapy in other cancers is being investigated in advanced thyroid cancer with pre-clinical work to pave way for human trials.

Combination Therapies: These is also a key trend in therapy of aggressive thyroid cancers, ie. the combination of several agents. For example, co-targeting TKIs with MEK inhibitors, mTOR inhibitors to circumvent towards resistance mechanisms. BRAF-mutant ATCs in particular have been responsive to some of these combinations such as dabrafenib/trametinib