Optimal use of lenvatinib in the treatment of advanced thyroid cancer

Abstract

The development of orally active, multitargeted kinase inhibitors (MKIs) represents a significant advance in the treatment of progressive, metastatic thyroid cancer. Lenvatinib, an MKI targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-Kit, and RET, has shown efficacy in stabilizing previously progressive disease, with emerging evidence of a possible benefit in terms of overall survival. However, lenvatinib is associated with a side-effect profile similar to those of other MKIs that might affect the outcome of therapy. The aim of this review is to summarize the clinical efficacy and safety of MKIs in the treatment of advanced thyroid cancer in pivotal phase III trials. Common adverse events that may occur during lenvatinib therapy and their management are discussed, including conditions in which its administration should be temporarily withdrawn and resumed pending resolution of adverse events. We focus on data from a subanalysis of Japanese patients in the SELECT trial and in a post-marketing study in Japan. We suggest that lenvatinib is a valuable treatment option for advanced differentiated thyroid cancer. Monitoring and careful management of adverse events including supportive care are required to ensure continuation of therapy.

Optimal management of patients with hepatocellular carcinoma treated with lenvatinib

“…An angiotensin II receptor blocker might be a second choice. Depending on the systolic and diastolic pressures, hypertension may be managed by an increased dose of the antihypertensive or the addition of another antihypertensive (Table 4) [28]. Grade 1 or 2 events can be managed without interrupting lenvatinib therapy, but lenvatinib should be discontinued while managing Grade 3 events.…”

“…In the REFLECT study, the incidence of diarrhea was 39% (≥ Grade 3: 4%) in the lenvatinib group and 46% (≥ Grade 3: 4%) in the sorafenib group [25]. A prescription for loperamide can be provided to the patient before the start of lenvatinib treatment [28]. Clinicians should advise patients to report incidents of diarrhea so…”

“…Although the incidence is generally higher in the early phase of treatment, palmar-plantar erythrodysesthesia syndrome can also occur during Cycles 5-15 [26]. As recommended with sorafenib therapy [33], patients should be given guidance on prophylactic moisturizing with urea-based cream and should continue lenvatinib treatment as long as no pain occurs [28]. If pain does occur, lenvatinib treatment can be interrupted while the condition is treated with a steroid.…”

“…Dose interruption may also be appropriate for patients with a UPCR < 3.5 if other symptoms such as edema, pleural effusion, ascites, or increased blood creatinine levels are observed. After the proteinuria is improved to Grade 0 or 1, lenvatinib treatment can be resumed [28].…”

Management of recurrent or metastatic thyroid cancer

“…The procedures for these adverse events have been reported. 16 While most adverse events are manageable using established procedures, management of the proteinuria related to this treatment has not been established, and although drug withdrawal results in a significant reduction, persistence is common. A reduction in intraglomerular pressure with angiotensin II receptor blockers or ACE inhibitors may improve proteinuria.…”