Lenvatinib: A Review in Refractory Thyroid Cancer

Area of Science:

• Oncology
• Pharmacology

Background:

• Differentiated thyroid cancer (DTC) that is refractory to radioiodine treatment (RR-DTC) presents a significant clinical challenge.
• Lenvatinib, a multi-targeted tyrosine kinase inhibitor (TKI), targets key signaling pathways including VEGF, FGF, PDGF, RET, and KIT, implicated in tumor growth.

Purpose of the Study:

• To evaluate the efficacy and safety of lenvatinib in patients with locally recurrent or metastatic progressive, radioiodine-refractory differentiated thyroid cancer (RR-DTC).

Main Methods:

• The Phase 3 SELECT study was a randomized, double-blind, multinational trial comparing lenvatinib to placebo in patients with RR-DTC.
• Key endpoints included progression-free survival (PFS) and overall response rate (ORR).

Main Results:

• Lenvatinib demonstrated a significant improvement in median PFS and ORR compared to placebo in patients with RR-DTC.
• The PFS benefit was consistent across subgroups, including those with prior VEGF-targeted therapy and regardless of BRAF or RAS mutation status.
• Hypertension was the most frequent treatment-related adverse event, generally manageable and rarely leading to discontinuation.

Conclusions:

• Lenvatinib is an effective and generally well-tolerated treatment option for patients with RR-DTC.
• It offers an acceptable alternative to sorafenib, the only other approved TKI for this indication.