Multikinase Inhibitors for the Treatment of Asymptomatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Global Noninterventional Study (RIFTOS MKI)

Abstract

Background: Sorafenib and lenvatinib are multi-kinase inhibitors (MKI) approved to treatfor patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry.Methods: International, prospective, open-label, non-interventional cohort study (NCT02303444). Eligible patients had asymptomatic, progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. The pPrimary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate treatment with an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry patients without a decision to initiate treatment with an MKI (Cohort 2). Based on interim analysis, it was decided to compare the cohorts Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients from 19 countries. The median duration of observation was 35.5 months (range <1-59.4). Of 344 MKI-treated patients, 209 received sorafenib, 191 received lenvatinib, and 19 received another MKI at some point. Median TTSP was 55.4 months (interquartile range [IQR] 18.6-NE) overall (N=647), 55.4 months (IQR 15.2-NE) in Cohort 1 (n=169), and 51.4 months (IQR 20.0-NE) in Cohort 2 (n=478). TTSP ≥36 months was achieved in 64.5% of patients overall, 59.5% of patients in Cohort 1, and 66.4% of patients in Cohort 2. Median post-progression survival in the FAS was 28.4 months and median Median overall survival (OS) from classification as RAI-R was 167 months and. Median median PFS from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months.

Real-world practice patterns and outcomes for RAI-refractory differentiated thyroid cancer

“…Eligible patients had asymptomatic RAI-R DTC and showed radiological progression, with at least one lesion ≥1 cm. RAI-R status was defined based on previously reported criteria ( 10 ). Patients who were previously treated with MKIs, enrolled in clinical trials, or in hospice care were excluded.…”

Recurrent Differentiated Thyroid Cancer: The Current Treatment Options

“…Brose et al [80] published an international, prospective, open-label, non-interventional cohort study in order to know when to start treatment with TKIs (sorafenib and lenvatinib) in patients with RAI-refractory DTC. There were 647 patients with a median duration of observation of 35.5 months (range < 1-59.4).…”

Anaplastic thyroid cancer: Pathogenesis, prognostic factors and genetic landscape (Review)

“…MKIs have the ability to act on two or more targets at the same time. MKIs such as sorafenib, axitinib, pazopanib and sunitinib have been studied in preclinical models, as well as a clinical trial, with promising results (21). The use of sorafenib also resulted in a progression-free survival time of ~5 months in a phase III clinical trial, with patients experiencing manageable toxicities in comparison with the placebo group (22).…”