Pre-therapeutic evaluation and practical management of cardiovascular and renal toxicities in patients with metastatic radioiodine-refractory thyroid cancer treated with lenvatinib

ABSTRACT

Introduction

Multi-receptor tyrosine kinase inhibitors with anti-angiogenic activity, particularly lenvatinib, have become the standard treatment for radioiodine-refractory metastatic differentiated thyroid cancer but are associated with a high incidence of toxicity. Although patients treated with lenvatinib have been shown to have a significant improvement in progression-free survival, lenvatinib-associated toxicity may result in dose reductions, dose interruptions or even complete lenvatinib withdrawal, compromising anti-tumor efficacy.

Areas covered

The article covers the main cardiological and renal toxicities of lenvatinib, including hypertension, prolonged QT interval, heart failure, arterial and venous thromboembolic events, proteinuria and renal failure, and proposes appropriate management of these events during lenvatinib therapy. We performed a literature review of cardiovascular and renal toxicities of Lenvatinib in radioiodine-refractory differentiated thyroid cancer. We discussed prophylactic and therapeutic management for each toxicity based on literature and clinical expertise.

Expert opinion

Specific pre-therapeutic evaluation and close monitoring of patients treated with lenvatinib is necessary to prevent and detect cardiovascular and/or renal toxicities early, and to propose appropriate management. Oncologists who treat patients with lenvatinib should know how to monitor and treat these adverse events, and when to ask for the advice of a specialist (cardiologist or nephrologist).

KEYWORDS:

• Antiangiogenic treatment
• hypertension
• lenvatinib
• proteinuria
• radioiodine-refractory thyroid cancer
• toxicities
• renal
• cardiovascular
• tyrosine kinase inhibitors

Article highlights

• Cardiovascular and renal toxicities are the most common toxicities in patient treated with lenvatinib

• Oncologists should have a strategy to prevent and manage those toxicities in collaboration with cardiologist and/or nephrologist if necessary

• Most patients experience arterial hypertension on lenvatinib, which should be managed promptly with anti-hypertensive drugs according to recommendations

• Proteinuria and renal function should be monitored and a renal biopsy should be discussed in case of significant disturbance

• QTc interval should be measured regularly on EKGs and risk factors of QT prolongations should be avoided (ionic abnormalities, associated medication prolonging the QT interval)

• In case of severe cardiovascular or renal adverse effects, the resumption of lenvatinib should be discussed with cardiologist and/or nephrologist according to the benefit/risk ratio

Acknowledgments

Editorial assistance in the preparation of this article was provided by Newmed Publishing Ltd., and by Nathalie Charbonnier, with financial support from Eisai.

Declaration of interests

J Wassermann received an honoraria from Eisai, Bayer, and Lilly, CI Bagnis has IB personal fees from Eisai, L Leenhardt reports travel expenses and personal fees from Eisai, S Edhery has personal fees from Eisai, C Buffet receives travel expenses and personal fees from EISAI and Lilly. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer is a principal Investigator in Eisai phase II and III trials with lenvatinib in thyroid carcinoma (E7080-G000-201, E7080-G000-303, and E7080-G000-604 studies), consultant for Ewo Pharma. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.

Author contribution statement

J Wassermann: Conceptualization, methodology, supervision, visualization, writing–original draft, writing–review and editing. CI Bagnis: Conceptualization, methodology, visualization, writing–original draft, writing–review and editing. L Leenhardt: Conceptualization, methodology, visualization, writing–review and editing. S Ederhy: Conceptualization, methodology, visualization, writing–original draft, writing–review and editing. C Buffet: Conceptualization, methodology, supervision, visualization, writing–review and editing

Additional information

Funding

This paper was funded by Eisai.