Lenvatinib plus pembrolizumab: the next frontier for the treatment of hepatocellular carcinoma?

ABSTRACT

Introduction

While sorafenib monotherapy represented the mainstay of medical treatment for advanced hepatocellular carcinoma (HCC) patients for more than a decade, novel agents and combination therapies have recently produced unprecedented paradigm shifts. The combination of lenvatinib plus pembrolizumab is now being evaluated as a front-line treatment in advanced HCC patients; early phase clinical trials have already reported promising results.

Areas covered

This paper reviews the combination of lenvatinib plus pembrolizumab for the treatment of advanced HCC. The preclinical rationale and completed and ongoing trials are examined and later, the authors reflect on biomarkers of predictive of response to immune-based combinations and future treatment decision-making on the basis of tolerability and clinical benefits provided by these novel therapeutics. A literature search was conducted in April 2021 of Pubmed/Medline, Cochrane library and Scopus databases; moreover, abstracts of international cancer meetings were reviewed.

Expert opinion

The landscape of new agents and combinations continues to expand. Recently, immune-based combinations have reported important results in advanced HCC, as witnessed by the landmark IMbrave150 trial. Based on the promising results of early phase clinical trials, lenvatinib plus pembrolizumab has the potential to represent a novel treatment option in this setting.

KEYWORDS:

• Hepatocellular carcinoma
• HCC
• immunotherapy
• lenvatinib
• pembrolizumab
• liver cancer
• immune checkpoint inhibitors
• clinical trials

Article highlights

• Immune checkpoint inhibitors (ICIs) have been explored as first-line treatment in unresectable HCC, as monotherapy or in combination with other anticancer agents.

• The recent results of the IMbrave150 trial have represented a historical step forward, with atezolizumab plus bevacizumab representing the new first-line treatment in advanced HCC.

• Additionally, several phase III trials assessing ICI-based combinations are still ongoing, and among these combinations, lenvatinib plus pembrolizumab has the potential to represent another emerging therapeutic option.

• Early phase clinical trials have already reported important results for lenvatinib plus pembrolizumab in advanced HCC, and ongoing studies will shed further light on this promising combination in this setting.

• The landscape of new agents and combinations continues to expand.

• Efforts should also be focused on the identification of biomarkers predictive of response to immune-based combinations, by guiding future treatment decisions on the basis of tolerability and clinical benefits provided by these novel therapeutic strategies.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.