Current treatment options for hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma remains a serious global disease. Its incidence is increasing. Standard procedures have been developed for each stage. The complexity of this disease shows that the selection of patients in stage 0/A for different types of surgical treatment is very complicated. Treatment methods of stage B, especially locoregional treatment represented by TACE (transarterial chemoembolization or radioembolization of TARE), radiofrequency ablation and others, move freely to lower and higher stages as adjunctive therapy. Lenvatinib can replace TACE with equal efficacy in cases where locoregional treatment cannot be used. Until 2016, the only systemic treatment option for stage C was sorafenib. Lenvatinib became a second-line drug to show non-inferiority to sorafenib in OS. Retrospective analyzes revealed that patients who responded to the treatment with lenvatinib or sorafenib had a median survival of over 22 months. Sequential treatment with sorafenib and regorafenib in the RESOURCE study with a median survival of more than 24 months was similar. Ramucirumab was effective only in patients with high AFP levels. The study demonstrated the importance of selecting patients according to prognostic factors (extrahepatic spread and vascular invasion). Second-line cabozantinib has shown the same benefit as regorafenib. In the second line, immunotherapy represented by anti PD-1 antibodies nivolumab and pembrolizumab was used. Sequential administration after sorafenib prolonged the median overall survival of about 22 months. We currently have sorafenib and lenvatinib in the first line, regorafenib, cabozantinib, ramucirumab (AFP 400 μg/L), pembrolizumab and nivolumab in the second line. The possibilities of monotherapy have been exhausted. The discovery of a synergistic effect of angiogenesis inhibitors, which convert a cold tumor into a hot one and facilitate the efficacy of anti-PD-1 / anti-PDL-1 antibodies, has led to a highly effective combination therapy. In study IMbrave150, the combination of atezolizumab and bevacizumab was successfully used compared to sorafenib in the first-line treatment. Additional studies are currently underway using other tyrosin kinase inhibitors - regorafenib, lenvatinib and cabozantinib - in combination with nivolumab, ipilimumab and pembrolizumab. This development of treatment at all stages evoked with renewed urgency the need to find a suitable way to search for the early stages of HCC and to create a more effective system for selecting patients for the most appropriate treatment.