Sorafenib-based combination as a first line treatment for advanced hepatocellular carcinoma: a systematic review of the literature

Background: Hepatocellular carcinoma is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Advanced HCC is a distinct disease entity with limited approved treatment options and grave prognosis. So, we will explore in this systematic review the value of using sorafenib-based combination in this poor prognosis subset of HCC.

Methods: PubMed, Medline, the Cochrane Library, trip database and Google Scholar were searched using the terms "Hepatocellular carcinoma" OR "Hepatoma" or "Liver cancer" AND "systemic anticancer therapy" AND "Sorafenib" and specifying only English literature. Outcomes of interest included progression free survival and overall survival (PFS and OS), tumor response, and toxicities.

Results: A total of 17 potentially relevant trials was identified, of which 9 studies were excluded. Hence, eight trials involving 272 patients were included. Median PFS was reported in 6 out of the 8 trials ranging from 3.7 to 7.5 months. Median OS was reported in 6 out of the 8 studies ranging from 7.4 to 40.1 months. The DCR was reported in the 8 studies, ranging from 48.7% to 76%. Frequently reported Grade 3/4 toxicities were increased AST/ALT, fatigue, hypertension, hand foot skin reaction and diarrhea. However, some chemotherapy-specific side effects were noted in some studies.

Conclusions: The current evidence from the available clinical trials suggests that sorafenib-based combination with some anticancer agents (especially mTOR inhibitors) could be a more effective and tolerable treatment for advanced HCC in the future. However, such sorafenib-based combination cannot be recommended outside the setting of clinical trials.