Hepatocellular Carcinoma: An Overview of the Changing Landscape of Treatment Options

Abstract

Andreas Koulouris,1 Christos Tsagkaris,2 Vasiliki Spyrou,3 Eleni Pappa,4 Aikaterini Troullinou,2 Michail Nikolaou5 1Resident of Medical Oncology, University General Hospital of Heraklion, University of Crete, Crete, Greece; 2Medical School, University of Crete, Crete, Greece; 3Hygeia Hospital, Athens, Greece; 4Medical School, National and Kapodistrian University of Athens, Athens, Greece; 5 1st Oncology Department, “Saint Savas” Anticancer - Oncology Hospital, Athens, GreeceCorrespondence: Michail Nikolaou 1st Oncology Department, “Saint Savas” Anticancer - Oncology Hospital, Athens, GreeceEmail [email protected]: The last three years have seen remarkable progress in comprehending predisposing factors and upgrading our treatment arsenal concerning hepatocellular carcinoma (HCC). Until recently, there were no means to withstand the progression of viral hepatitis-associated liver cirrhosis to HCC. A deeper understanding of the molecular mechanism of the disease, the use of biomarkers, and the follow-up, allowed us to realize that conventional chemotherapy failing to increase survival in patients with advanced HCC tends to be exiled from clinical practice. Multi-kinase inhibitors (TKIs) such as sorafenib, lenvatinib targeting mainly the vascular endothelial growth factor receptors 1– 3 VEGFRs 1– 3 provided until recently the standard of care for these patients, as first- or second-line treatment. Since May 2020, the atezolizumab plus bevacizumab combination (immunotherapy plus anti-VEGF) has become the new reference standard in first-line HCC treatment. Additionally, anti-programmed cell death protein 1 (anti-PD-1) immunotherapy can be used as a second-line treatment following first-line treatment’s failure. Phase III clinical trials have recently suggested the efficacy of novel anti-angiogenic factors such as cabozantinib and ramucirumab as a second-line treatment option. With considerations about toxicity arising, clinical trials are investigating combinations of the aforementioned targeted therapies with immunotherapy as first-line treatment. This paper aims to perform a systematic review describing the evolving treatment options for HCC over the last decades, ranging from neoadjuvant treatment to systemic therapy of advanced-stage HCC. With the landscape of HCC treatment shifting towards novel agents the forming of a new therapeutic algorithm for HCC seems to be imperative.Keywords: hepatocellular carcinoma, immunotherapy, targeted therapy, tyrosine kinase inhibitors, biomarkers

Keywords

• hepatocellular carcinoma
• immunotherapy
• targeted therapy
• tyrosine kinase inhibitors
• biomarkers