Expert consensus on the management of adverse events in patients receiving lenvatinib for hepatocellular carcinoma

Lenvatinib is an oral multikinase inhibitor approved for use as first‐line treatment for patients with advanced hepatocellular carcinoma (HCC). However, like other agents in this drug class, lenvatinib is associated with clinically important adverse events (AEs) that could adversely affect patient outcomes. Hypertension, diarrhea, decreased appetite/weight, hand–foot skin reaction, and proteinuria are among the most common AEs associated with lenvatinib therapy. This article provides strategies for the effective management of lenvatinib‐associated AEs based on the expert opinion of authors and currently available literature. Due to the high risk of AEs in patients receiving lenvatinib, prophylactic measures and regular monitoring for AEs are recommended. Lenvatinib dose interruption, adjustment, or discontinuation of treatment may be required for patients who develop AEs. For grade 1 or 2 AEs, dose interruption is generally not required. For persistent or intolerable grade 2 or 3 AEs, lenvatinib treatment should be interrupted until symptoms improve/resolve to grade 0–1 or baseline levels. Thereafter, treatment should be resumed at the same or a lower dose. Disease progression may occur in patients who do not initially respond to treatment or receive a suboptimal lenvatinib dose following dose reduction, resulting in lack of efficacy. Therefore, to derive maximum treatment benefit and ensure long‐term disease control, lenvatinib should be maintained at the highest possible dose when managing AEs. To conclude, lenvatinib‐associated AEs can be managed with prophylactic measures, regular monitoring and symptomatic management, which can ensure continued treatment and maximum survival benefit in patients with advanced HCC receiving first‐line lenvatinib therapy.