Efficacy and Safety of Tyrosine Kinase Inhibitors in Downstaging and Palliation in Patients with Advanced Differentiated Thyroid Cancer - A Multicentre study

Abstract

Thyroid cancer (TC) is the most common endocrine malignancy worldwide, with differentiated thyroid cancer (DTC) comprising the majority of cases. Surgical treatment of locally advanced DTC can be challenging, prompting the exploration of tyrosine kinase inhibitors (TKIs) to downstage the disease burden before surgery. Sorafenib and Lenvatinib have shown promising response rates in managing refractory DTC. This study aimed to assess the efficacy and safety profile of Sorafenib and Lenvatinib in the Indian population for locally advanced DTCs. A retrospective multicentric study across three Indian Endocrine surgery centres evaluated the efficacy and safety of Sorafenib and Lenvatinib in locally advanced DTC. Data from 45 patients with DTC, including demographics, treatment details, adverse effects, and outcomes, were analysed. Sorafenib and Lenvatinib demonstrated substantial efficacy, with 70.8% and 42.9% of patients achieving a partial response, respectively (p = 0.226). Median progression-free survival (PFS) was 30.15 months for Sorafenib and 35.54 months for Lenvatinib (p = 0.868). Overall survival (OS) was 28.23 months for Sorafenib and 34 months for Lenvatinib (p < 0.722). Adverse events (AEs) were common, with Sorafenib associated with higher AE rates (72% vs. 35.7% for Lenvatinib) and hand-foot syndrome being the most prevalent (p = 0.027). However, AEs did not significantly differ in causing drug discontinuation or dose reduction between the two TKIs. Sorafenib and Lenvatinib show promising results in managing advanced DTCs, with substantial efficacy and manageable AEs. Further research, including prospective studies with larger cohorts, is needed to validate these findings and optimize treatment strategies for advanced DTCs.

Keywords: Efficacy and safety of Tyrosine kinase inhibitors; Inoperable differentiated thyroid cancer; Lenvatinib; Radioactive refractory differentiated thyroid cancer; Sorafenib.