Lenvatinib for Anaplastic Thyroid Cancer and Lenvatinib-Induced Thyroid Dysfunction

Abstract

Background: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor that has an anticancer action in patients with differentiated thyroid cancer that is refractory to radioiodine. Knowledge of the efficacy and safety of lenvatinib in patients with anaplastic thyroid cancer (ATC) is limited. Tyrosine kinase inhibitors frequently cause hypothyroidism, but the incidence of hypothyroidism with lenvatinib is unclear. Objectives: We conducted a retrospective study to investigate the efficacy and safety of lenvatinib in ATC. Methods: Five patients with unresectable ATC were enrolled. Lenvatinib 24 mg once daily was administered until disease progression, unmanageable toxicity, withdrawal, or death occurred. We retrospectively analyzed the objective response rate (ORR), time to progression (TTP), overall survival, and safety. Results: Three of the 5 patients (60%) had a partial response, and 5 (40%) had stable disease. The ORR was 60%. Median TTP was 88 days, and overall survival was 165 days. Hypothyroidism was a common treatment-related adverse effect; 4 patients (80%) had hypothyroidism of any grade. These 4 patients had not undergone total thyroidectomy prior to lenvatinib administration, and the other patient had undergone total thyroidectomy. Treatment-related adverse effects of any grade were hypertension in 80% of patients, diarrhea in 40%, fatigue in 80%, and decreased appetite in 80%. Conclusions: Lenvatinib is an effective treatment and may improve the prognosis of unresectable ATC. Four of the 5 patients had hypothyroidism, which may have been associated with treatment-induced injury of the thyroid gland. There were many treatment-related adverse effects, most of which were manageable by dose modification and medical therapy.

Multikinase Inhibitor Treatment in Thyroid Cancer

“…The different types of cancers like RAI-refractory DTC, MTC, and ATC show a diversity in outcomes. Not surprisingly, ATC shows the worst survival rates, with an OS of 165 days [44] and 166 days [33] and a PFS of 7.4 months [49]. These results support the current knowledge regarding ATC having a much worse prognosis compared to the other types of thyroid cancer, even when treated with MKIs.…”

“…Three studies investigated the effect of lenvatinib in patients with ATC: Takahashi et al [49] measured a PFS of 7.4 months. Koyama et al [44] reported an OS of 165 days and an RR of 60%. Moreover, Iwasaki et al [33] published an OS of 166 days and an RR of 17.4%.…”

Survival With Lenvatinib for the Treatment of Progressive Anaplastic Thyroid Cancer: A Single-Center, Retrospective Analysis

“…Retrospective data can be used to bridge the current knowledge gap, and provide much-needed data for clinicians looking to improve outcomes for their patients. Previous retrospective analyses in Japanese patients have indicated that lenvatinib is associated with disease control rates (clinical response or stable disease) of 44% ( 21 ) to 100% ( 22 ), and OS times of 165 ( 22 ) to 166 ( 21 ) days, although tumor volumes were not evaluated. While it is not possible to directly compare studies due to the heterogeneity of the enrolled patients and the differing therapeutic procedures used, the treatment regimen used in our institute was able to produce a relatively lengthy median OS of 230 days, and additionally demonstrated a direct, measurable impact on tumor volume in almost 90% of patients.…”

Therapeutic advances in anaplastic thyroid cancer: a current perspective

“…A retrospective analysis of ATC patients treated with Lenvatinib resulted in partial responses (PR) in 60% (3/5) of patients whereas 40% (2/5) experienced stable disease with manageable toxicity. In addition, the observed objective response rate (ORR) was 60% with median time to progression (TTP) and overall survival (OS) as 88 and 165 days respectively [ 30 ].…”