The hepatocellular carcinoma (HCC) treatment landscape changed a decade ago, 
with sorafenib demonstrating survival benefit in the first-line setting and 
becoming the first systemic therapy to be approved for HCC. More recently, 
regorafenib and nivolumab have received approval in the second-line setting 
after sorafenib, with further positive phase 3 studies emerging in the first 
line (lenvatinib non-inferior to sorafenib) and second line versus placebo 
(cabozantinib and ramucirumab). A key recommendation in the management of 
patients receiving sorafenib is to promote close communication between the 
patient and the physician so that adverse events (AEs) are detected early and 
severe AEs can be prevented. Sorafenib-related AEs have been identified as 
clinical biomarkers for sorafenib efficacy. Healthcare professionals have become 
more efficient in managing AEs, identifying patients who are likely to benefit 
from treatment, and assessing response to treatment, resulting in a trend 
towards increased overall survival in the sorafenib arms of clinical studies. 
The rapidly changing treatment landscape due to the emergence of new treatment 
options (sorafenib and lenvatinib equally effective in first line; regorafenib, 
cabozantinib, and ramucirumab showing OS benefit in second line with nivolumab 
approved by the FDA based on response rate) underscores the importance of 
re-assessing the role of the first approved systemic agent in HCC, sorafenib.