The Trend of the Treatment of Advanced Hepatocellular Carcinoma: Combination of Immunotherapy and Targeted Therapy

Abstract

Hepatocellular carcinoma (HCC) is a common type of tumor worldwide. The development of systemic treatment of advanced HCC has remained stagnant for a considerable period. During the last years, a series of new treatment regimens based on the combination of immunotherapeutic drugs and targeted drugs have been gradually developed, increased the objective response rate (ORR), overall survival (OS), and progression free survival (PFS) of HCC patients. Among the different combination therapy groups, atezolizumab plus bevacizumab and sintilimab plus IBI-305 seem to have unique advantages, while head-to-head comparisons are still needed. A comprehensive understanding of the developments, the ongoing clinical trials and the mechanisms of combination of immunotherapy and targeted therapy might lead to the development of new combination strategies and solving current challenges such as the molecular biomarkers, the clinical administration order of drugs and the second-line treatments after combination therapy.

Keywords: Combination therapy; Hepatocellular carcinoma; Immunotherapy; Targeted drugs.

Fig. 1

Timeline of systemic treatments for advanced HCC. Positioned above the time axis are the first and second-line drugs approval by the U.S. FDA and the China NMPA, and the drugs in red are immune checkpoint inhibitors; positioned below the time axis are the first line treatments recommended by the NCCN guidelines, and the red marks the differences between versions

Fig. 2

Mechanisms of combination immune checkpoint inhibitors and targeted drugs. This involves the concerted suppression of abnormal vascular proliferation, modulation of PD-1 expression, and restructuring of the tumor microenvironment, collectively fostering a synergistic sensitization effect