First-line systemic therapy

Historically, sorafenib (a multikinase inhibitor) has been the standard of care for patients with advanced HCC and intact liver function (Child-Pugh class A) who were not candidates for locoregional therapy. This standard was based on the results of the SHARP trial, which showed improved OS for patients who received sorafenib compared with placebo (10.7 vs. 7.9 months; hazard ratio [HR], 0.69; P < .001). However, treatment-related adverse events may make adherence to sorafenib regimens difficult, especially in a population with concurrent liver disease. Since 2018, additional drugs and drug combinations, including atezolizumab-bevacizumab and durvalumab-tremelimumab, have resulted in improved OS when compared with sorafenib, resulting in U.S. Food and Drug Administration (FDA) approval. Other regimens have demonstrated noninferiority when compared with sorafenib, including lenvatinib (a multikinase inhibitor) and immunotherapy monotherapy. In choosing first-line therapy, survival data, response rates, bleeding risk (i.e., active varices), and the likelihood of tolerating individual therapies should be considered.