Critique on “Real-World Effectiveness of First-Line Lenvatinib Therapy in Advanced Hepatocellular Carcinoma: Current Insights” [Letter]

Dear editor

Tiago Biachi de Castria and Richard D Kim have done excellent work on the article titled “Real-World Effectiveness of First-Line Lenvatinib Therapy in Advanced Hepatocellular Carcinoma: Current Insights” published in the Dove Medical Press journal. This article offers a comprehensive analysis of lenvatinib as a first-line therapy for advanced hepatocellular carcinoma (HCC), presenting significant findings on its efficacy. However, there are several critical areas that require further discussion and clarification.¹

One of the primary concerns is the inadequate emphasis on the adverse effects associated with lenvatinib. The article does not sufficiently highlight the spectrum and severity of adverse events that patients might experience. For instance, a meta-analysis has indicated that the most common adverse effects of lenvatinib include hypertension (36.8%), decreased appetite (36.4%), fatigue (34.5%), palmar-plantar erythrodysesthesia syndrome (PPES) (29.4%), decreased weight (29.1%), proteinuria (25.6%), diarrhoea (24.6%), and hypothyroidism (22.5%).² These adverse events are not trivial and can significantly impact the patients’ quality of life and treatment compliance. Moreover, there have been case reports depicting the association of tumour lysis syndrome with its use.³ Therefore, it is imperative for future studies and reports to thoroughly address and manage these adverse effects to provide a balanced view of lenvatinib therapy.

Moreover, the article does not provide clear guidelines on the clinical scenarios where lenvatinib should be preferred over other tyrosine kinase inhibitors (TKIs), such as sorafenib. Dipasquale et al have highlighted that the choice between lenvatinib and sorafenib should be guided by specific selection criteria, including patient’s clinical characteristics and prognostic factors. It is crucial for practitioners to have clear, evidence-based guidelines on when to opt for lenvatinib, considering factors like the presence of chronic hepatitis B virus (HBV) infection and alpha-fetoprotein (AFP) levels, which may favour the use of lenvatinib over sorafenib.⁴ Studies in the past have shown that Lenvatinib shall be preferred over other AKIs when HBV is the cause, <50% of liver involvement with no bile duct or portal vein involvement, age less than 45 years and AFP >200ng/mL. Additionally, the fast approval of atezolizumab plus bevacizumab for advanced HCC has introduced new considerations into the therapeutic landscape, making the choice of TKIs even more complex.

In conclusion, while the article provides valuable insights into the effectiveness of lenvatinib, it would benefit from a more detailed discussion on the adverse effects and clearer guidelines on its use relative to other treatments. Addressing these aspects will enhance the clinical utility of the findings and support better patient outcomes.