Is There Still a Place for Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma at the Time of Immunotherapies? A Focus on Lenvatinib

Simple Summary The combination of atezolizumab and bevacizumab has changed the therapeutic algorithm of advanced hepatocellular carcinomas. Therefore, the place of tyrosine kinase inhibitors, and among them, lenvatinib, which exhibits promising antitumour activity compared to other TKIs, needs to be redefined. Lenvatinib is still an option in case of contra-indication of immunotherapy or anti-vascular endothelial growth factor (anti-VEGF), but its place can also be discussed in second-line treatment. Otherwise, emerging strategies are currently being studied to assess the efficacy of the combination of lenvatinib with immunotherapy or loco-regional treatment for advanced HCC, as well as the efficacy of lenvatinib alone or in combination at earlier stages of the disease. The aim of this review was to define potential indications for lenvatinib treatment in different clinical situations of hepatocellular carcinoma. The systemic treatment of hepatocellular carcinoma is changing rapidly. Three main classes of treatment are now available. Historically, multi-targeted tyrosine kinase inhibitors (TKIs) (sorafenib and lenvatinib as first-line; regorafenib and cabozantinib as second-line) were the first to show an improvement in overall survival (OS). Anti-vascular endothelial growth factor (anti-VEGF) antibodies can be used in first-line (bevacizumab) or second-line (ramucirumab) combination therapy. More recently, immuno-oncology (IO) has profoundly changed therapeutic algorithms, and the combination of atezolizumab-bevacizumab is now the first-line standard of care. Therefore, the place of TKIs needs to be redefined. The objective of this review was to define the place of TKIs in the therapeutic algorithm at the time of IO treatment in first-line therapy, with a special focus on lenvatinib that exhibits one of the higher anti-tumoral activity among TKI in HCC. We will discuss the place of lenvatinib in first line (especially if there is a contra-indication to IO) but also after failure of atezolizumab and bevacizumab. New opportunities for lenvatinib will also be presented, including the use at an earlier stage of the disease and combination with IOs.

Automated summary

The use of atezolizumab and bevacizumab in advanced hepatocellular carcinomas has changed the therapeutic approach, emphasizing the need to redefine the role of tyrosine kinase inhibitors, particularly lenvatinib. This review aims to explore potential indications for lenvatinib treatment in different clinical scenarios and highlights the evolving landscape of systemic treatment options in hepatocellular carcinoma.