Immune-checkpoint inhibitors for advanced hepatocellular carcinoma : a synopsis of response rates

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer‐related death worldwide. A first‐line standard of care (SoC), sorafenib results in median overall survival (OS) of 12 months in Child‐Pugh class A patients, and 6 months in Child‐Pugh class B patients with objective response rates (ORR) 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 regards 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.