Johann von Felden1. 1. I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Abstract
PURPOSE OF REVIEW: Despite major therapeutic improvements in most cancer entities, hepatocellular carcinoma (HCC) has remained a dismal disease. In fact, incidence and mortality are increasing in many parts of the world, including the United States. Given that a number of systemic agents has recently been tested positive in phase 3 clinical trials, the objective of this review is to summarize the current treatment landscape for advanced HCC. RECENT FINDINGS: Following the positive SHARP trial in 2008, sorafenib has been the only systemic agent for advanced HCC for almost a decade. However, in first line, lenvatinib was tested noninferior to sorafenib, and most recently, the combination of atezolizumab with bevacizumab was tested superior to sorafenib. In second line, regorafenib, cabozantinib, and ramucirumab (the latter for patients with AFP ≥400 ng/ml) have shown prolonged overall survival compared with placebo. SUMMARY: Systemic treatment options for advanced HCC have substantially increased over the past years. The combination of atezolizumab and bevacizumab will likely become the new standard of care as it is the first treatment to report improved overall survival compared with sorafenib and the first, and so far only, positive phase 3 clinical trial for an immune-checkpoint inhibitor-containing regimen in advanced HCC.
PURPOSE OF REVIEW: Despite major therapeutic improvements in most cancer entities, hepatocellular carcinoma (HCC) has remained a dismal disease. In fact, incidence and mortality are increasing in many parts of the world, including the United States. Given that a number of systemic agents has recently been tested positive in phase 3 clinical trials, the objective of this review is to summarize the current treatment landscape for advanced HCC. RECENT FINDINGS: Following the positive SHARP trial in 2008, sorafenib has been the only systemic agent for advanced HCC for almost a decade. However, in first line, lenvatinib was tested noninferior to sorafenib, and most recently, the combination of atezolizumab with bevacizumab was tested superior to sorafenib. In second line, regorafenib, cabozantinib, and ramucirumab (the latter for patients with AFP ≥400 ng/ml) have shown prolonged overall survival compared with placebo. SUMMARY: Systemic treatment options for advanced HCC have substantially increased over the past years. The combination of atezolizumab and bevacizumab will likely become the new standard of care as it is the first treatment to report improved overall survival compared with sorafenib and the first, and so far only, positive phase 3 clinical trial for an immune-checkpoint inhibitor-containing regimen in advanced HCC.