Lenvatinib applicability in the therapeutic strategy of patients with hepatocellular carcinoma

The Expert Consensus on the management of lenvatinib tolerance in patients with hepatocellular carcinoma(HCC)was published(1).There,the authors discussed how possibly lenvatinib-related adverse events could be managed in aim to ensure continued lenvatinib therapy at the highest possible dose,and as a result to gain optimal benefit on survival of patients.In this editorial,the place of lenvatinib in HCC therapeutic strategies as well as its tolerance are reviewed and discussed.

Combination therapy for advanced hepatocellular carcinoma:do we see the light at the end of the tunnel?

Importance:Combination therapies of anti-PD-1 and anti-angiogenesis regimens are emerging rapidly and exhibit more promising anti-tumor efficacy for advanced hepatocellular carcinoma(HCC),and consistently it is the hotspot in clinical studies.Objective:To elaborate several issues which are warranted further consideration as more regimens are being investigated in combination therapies.Evidence Review:We searched PubMed,MEDLINE,Cochrane Library and Google Scholar by 2021 February for publications on combination therapies for HCC.Findings:Several clinical issues are worth reconsidering,such as the evaluation on appropriate primary endpoints in phase III clinical trials as for different practical problems,the translation of surrogate endpoint objective response rate(ORR)benefits into overall survival(OS)benefits,and whether conversion surgery contributes to initial expectations of long-term survival or not.New concepts in novel immunotherapy and targeted therapy in combination with loco-regional therapies may improve overall survival for HCC.Conclusions and Relevance for Reviews:Comprehensive understanding of the mechanism of immunotherapy and targeted therapy contributes to better prognosis of advanced HCC and more explorative combination therapies are needed.

Comparison and analysis of the efficacy of drug therapy for liver cancer

Hepatocellular carcinoma(HCC)is a poor prognosis tumor when not accessible to potentially curative treatments such as surgical resection,thermal ablations or liver transplantation.Systemic cytotoxic chemotherapies have shown inconsistent clinical benefit.In 2007,sorafenib,a tyrosine kinase inhibitor(TKI),was the first systemic therapy able to significantly improve the outcome of HCC patients non-eligible for curative or loco-regional therapies,despite a modest tolerance and low tumor objective response rate(ORR).Among the newer TKIs approved after 2017,lenvatinib was the first to show a striking ORR and demonstrate non-inferiority vs.sorafenib in the first-line setting.Furthermore,phase 3 trials showed the benefit of other TKIs,regorafenib and cabozantinib,and the anti-angiogenic ramucirumab monoclonal antibody,in systemic second-line therapy.Immune checkpoint inhibitors targeting PD1,achieved striking tumor shrinkage in some patients in monotherapy,seeming to be associated with exciting outcomes.Unfortunately,this occurred in too few patients to improve the median overall survival.More recently,the combination of anti-angiogenic drugs targeting the liver microenvironment with PD-1/PD-L1 inhibitors,such as the combination of bevacizumab and atezolizumab,proved to be substantially effective in phase 3,and other combinations of PD-1/PD-L1 and CTLA-4 inhibitors or TKIs have raised a lot of hopes for the systemic treatment of HCC.