Hepatocellular carcinoma (HCC) is the fourth most common cause of
cancer-related death worldwide. A first-line standard of care,
sorafenib results in median overall survival of 12 months in patients with Child-Pugh class A disease and 6 months in patients with Child-Pugh class B disease with objective response rates (ORRs) not exceeding 19%. These low efficacy rates have driven research on alternative therapeutic options, particularly
immune-checkpoint inhibitors (ICIs). We reviewed the response rates (estimated by RECIST 1.1 criteria) across patients with advanced HCC treated with ICIs in phase I-IV clinical trials published between December 2012 to December 2020; 17 reports were identified as eligible and included in the quantitative analysis. Within the selected studies,
pembrolizumab +
lenvatinib reached the highest absolute ORR (36%), with first-line
atezolizumab +
bevacizumab showing the second highest ORR (27.3%). With regard to second-line
therapy,
nivolumab +
ipilimumab reached an ORR of 32%, and
pembrolizumab alone resulted in an ORR of 17% among
sorafenib-experienced patients with advanced HCC. In summary, current studies show high response rates of ICIs in patients with advanced HCC. Nonetheless, further studies are required in the second-line setting to further evaluate ICI therapeutic superiority. Finally, it is of particular interest to examine the therapeutic potential of ICIs for patients with decompensated
liver disease (Child-Pugh class C), currently not eligible for any systemic
therapy. IMPLICATIONS FOR PRACTICE:
Immune-checkpoint inhibitors (ICIs) can provide high objective response rates (ORR, estimated with RECIST 1.1. criteria) when used as first-line treatment in advanced
hepatocellular carcinoma, particularly
pembrolizumab +
lenvatinib (ORR 36%) or
atezolizumab +
bevacizumab (ORR 27.3%). In
sorafenib-experienced patients,
nivolumab +
ipilimumab (ORR 32%) provided the highest ORR among ICI-based regimens. These findings emphasize high therapeutic potential of ICI-based
therapies in patients with advanced
hepatocellular carcinoma, although further studies are required to further validate and define their role in this context.