The role of lenvatinib in different types of thyroid cancer

Radioiodine-refractory thyroid cancer represents a major clinical challenge, with limited therapeutic options and a poor prognosis. Lenvatinib, an oral multikinase inhibitor, is approved as first-line treatment for differentiated thyroid cancer refractory to radioactive iodine (RAIR-DTC), and has demonstrated significant efficacy in clinical trials as well as in real-world settings.

In this review article, the authors provide a comprehensive analysis of lenvatinib's role across various thyroid cancer subtypes. In RAIR-DTC, lenvatinib has shown a high objective response rate and a significant increase in progression-free survival. In cases of poorly differentiated thyroid carcinoma, available data are also encouraging, indicating relevant clinical activity. In contrast, the efficacy of lenvatinib monotherapy in anaplastic thyroid carcinoma is limited; however, its combination with immunotherapy—particularly pembrolizumab—has yielded promising results. Regarding medullary thyroid carcinoma, existing evidence is still scarce and based solely on phase II trials.

Despite its effectiveness, lenvatinib is associated with frequent and relevant adverse events, including hypertension, fatigue, diarrhoea, and proteinuria. The decision to initiate lenvatinib treatment should be individualized, taking into account disease aggressiveness and extent, patient performance status, presence of symptoms, and documented tumour progression.

Authors and Affiliations:

Catarina Regala¹, Tiago Nunes da Silva¹, Valeriano Leite¹

¹Department of Endocrinology, Francisco Gentil Portuguese Institute of Oncology, Lisbon, Portugal

Abstract:

Background: Advanced and progressive thyroid cancer (TC) such as radioiodine-refractory thyroid cancer (RAIR-TC), presents a significant clinical challenge due to its poorer prognosis and limited therapeutic options. Lenvatinib is an oral multi-targeted tyrosine kinase approved as first line for the treatment of RAIR-TC.

Methods: We provide a comprehensive review of lenvatinib in the management of advanced thyroid cancer including RAIR-TC, poorly differentiated (PDTC), anaplastic (ATC) and medullary thyroid carcinoma (MTC).

Results: Lenvatinib demonstrated beneficial outcomes in treating RAIRTC with most patients   achieving either partial response or stable disease, which led to its approval by regulatory agencies worldwide. In PDTC, lenvatinib demonstrated potential therapeutic usefulness, whereas its efficacy as a monotherapy in ATC has yielded less consistent outcomes. However, in ATC the combination of lenvatinib with immune check point inhibitors (such as pembrolizumab) seem promising. In MTC, the available data is limited to phase II studies. Adverse effects (AEs) of any grade occur in almost all lenvatinib-treated patients and mostly have a time specific sequence of occurrence. Therapy discontinuations due to adverse events are not uncommon, and in some cases, drug-related fatalities may occur.

Conclusions: Lenvatinib demonstrated clinical efficacy and safety in both clinical trials and real-world studies for the treatment of patients with different types of thyroid cancer.

Journal: Minerva Endocrinology

Link: https://www.minervamedica.it/en/journals/minerva-endocrinology/article.php?cod=R07Y9999N00A25073001