Immune-Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Synopsis of Response Rates

Dmitrii Shek; Scott A Read; Adnan Nagrial; Matteo S Carlino; Bo Gao; Jacob George; Golo Ahlenstiel

doi:10.1002/onco.13776

Immune-Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Synopsis of Response Rates

Oncologist. 2021 Jul;26(7):e1216-e1225. doi: 10.1002/onco.13776. Epub 2021 Apr 21.

Authors

Dmitrii Shek^{1

2

3}, Scott A Read^{1

2

3}, Adnan Nagrial^{3

4

5}, Matteo S Carlino^{3

4

5

6}, Bo Gao^{3

4}, Jacob George^{2

4

5}, Golo Ahlenstiel^{1

2

3

5}

Affiliations

¹ Blacktown Clinical School, Western Sydney University, Sydney, New South Wales, Australia.
² Storr Liver Centre, Westmead Institute for Medical Research, Sydney, New South Wales, Australia.
³ Blacktown Hospital, Sydney, New South Wales, Australia.
⁴ Westmead Hospital, Sydney, New South Wales, Australia.
⁵ Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia.
⁶ Melanoma Institute Australia, Sydney, New South Wales, Australia.

Abstract

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.

Keywords: Atezolizumab; Hepatocellular carcinoma; Ipilimumab; Lenvatinib; Nivolumab; Pembrolizumab; Sorafenib.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Carcinoma, Hepatocellular* / drug therapy
Humans
Immune Checkpoint Inhibitors
Liver Neoplasms* / drug therapy
Sorafenib / therapeutic use

Substances

Immune Checkpoint Inhibitors
Sorafenib