Optimal therapy for patients with hepatocellular carcinoma and resistance or intolerance to sorafenib: challenges and solutions

Abstract

The only US Food and Drug Administration (FDA)-approved first-line systemic therapy for hepatocellular carcinoma (HCC) is sorafenib; however, resistance or intolerance to sorafenib is unfortunately common. In this review, we briefly describe systemic therapies that can be considered for patients with HCC who show resistance or intolerance to sorafenib. For all patients with HCC who need systemic therapy, we strongly advocate for participation in clinical trials. Cytotoxic chemotherapy plays a minor role in the treatment of advanced HCC, with some data supporting the use of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) and GEMOX (gemcitabine-oxaliplatin). Multi-target kinase inhibitors such as lenvantinib and regorafenib have recently met their primary endpoints as first- and second-line therapy, respectively, with regorafenib now representing the only FDA-approved drug for second-line treatment of HCC. Other targeted therapies remain under investigation, but results so far have not significantly changed clinical practice. Immunotherapy is an interesting area of research in the treatment of HCC with preclinical and early clinical data demonstrating exciting results; thus numerous investigational studies are currently focusing on immunotherapy in the treatment of HCC. While systemic treatment options in HCC remain a challenge for providers, in this review, we summarize the current literature and highlight areas of progress with respect to the treatment of patients with HCC and resistance or intolerance to sorafenib.

Identification and validation of potential key long noncoding RNAs in sorafenib-resistant hepatocellular carcinoma cells

“…Sorafenib, the most widely used drug for patients with non-resectable tumors, is the only FDA-permitted systemic therapy for HCC in the clinical first line (Ray & Sanoff, 2017).…”

EGFR and c-MET Cooperate to Enhance Resistance to PARP Inhibitors in Hepatocellular Carcinoma

“…There are currently no effective targeted therapies for the advanced HCC, which is the major form of liver cancer (19). For instance, the multikinase inhibitor sorafenib exhibits only moderate overall therapeutic efficacy (20). Future treatment approaches to improve the therapeutic efficacy in patients with HCC is expected to consist of combined targeted therapies based on the molecular classification of each patient.…”

Systemic treatments for hepatocellular carcinoma: challenges and future perspectives

“…As such, while waiting the approval of second-line therapies for HCC progressors, sorafenib could still be offered beyond radiological, but not symptomatic progression. Once second-line treatments will be available, the most appropriate management after sorafenib failure will have to be investigated in future large trials [ 54 ].…”