Kinase Inhibitors in the Treatment of Thyroid Cancer: Institutional Experience

Abstract

SUMMARY Although most patients with thyroid cancer have a favorable clinical course, some patients develop a more aggressive type of cancer and exhibit more rapid disease progression with worse prognosis. Those patients usually exhibit mutations of proteins such as tyrosine kinase enzymes that play a significant role in regulation of tumor proliferation and spreading. Development of targeted therapies is based on the inhibition of mutated kinases which are involved in the MAPK signaling pathway. The aim of this study was to present the initial results of clinical experience with kinase inhibitors in patients with metastatic differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), and medullary thyroid cancer (MTC) who exhibited rapid disease progression. A total of 17 adult patients (11 women, mean age 53.3 years) managed for progressive, metastatic disease were included in the study. Twelve patients with DTC and PDTC were previously tested for BRAF mutations, of whom nine that had tumor tissue negative for the BRAF V600E mutation received sorafenib, while three patients with tumors harboring the BRAF V600E mutation were treated with vemurafenib. Patients with MTC were treated with sunitinib, vandetanib, and sorafenib. Two patients with tumors harboring the BRAF mutation treated with vemurafenib showed restoration of radioiodine uptake. Most of patients showed significant improvement in disease status but of limited duration until disease progression. Although there was an improvement in progression-free survival, future research has to achieve a greater and longer-lasting response, probably by utilizing combined targeted therapy.

Tackling Thyroid Cancer in Europe—The Challenges and Opportunities

“…An adequate clinical trial framework (and appropriate funding) does not exist. Only limited research has been performed on combined treatments such as check-point inhibitors and tyrosine kinase inhibitors (TKIs) [ 31 , 32 ]. In addition, EU data protection rules impose limits on transatlantic data exchange, which inhibits joint academic trials.…”

Predictors of radioiodine (RAI)-avidity restoration for NTRK fusion-positive RAI-resistant metastatic thyroid cancers

“…TERT is not covered by this panel (personal communication with Dr Oliver Huillard) and was instead covered on ThyroSPEC testing. Unfortunately, five single-arm ( 6 , 7 , 14 , 22 , 23 ) and three uncontrolled retrospective studies ( 24 , 25 , 26 ) on MAPK inhibition of metastatic RAI-resistant thyroid cancer with BRAF , RAS, or no detected driver mutation for RAI re-sensitization do not provide any information regarding TERT mutation analysis. Therefore, in addition to the analysis of the driver mutation, future RAI re-sensitization studies should provide information regarding the TERT mutation status of the primary tumors, and if possible, the TDS gene expression.…”

Management of Progressive Radioiodine-Refractory Thyroid Carcinoma: Current Perspective

“…The efficacy of vemurafenib and dabrafenib (both BRAF inhibitors) in restoring RAI avidity has been studied in BRAF-mutated RAI-R TC patients, with similar results. [116][117][118] However, it was noticed that BRAFmutated TC showed worse response to redifferentiation therapies, 115 assuming the need of a stronger MAPK pathway inhibition in those patients, obtained by combining a BRAF-and a MEK-inhibitor. [119][120][121][122] The short-term schedule of these therapies (4-8 weeks in the majority of trials) could induce significantly lower toxicity in comparison with longterm MKI treatment, also reducing the economic burden of therapy.…”