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Kwee et al. Hepatoma Res 2022;8:32 Hepatoma Research
DOI: 10.20517/2394-5079.2022.58

Editorial Open Access

Immunotherapy biomarkers for HCC: contemporary

challenges and emerging opportunities

Sandi Kwee 1,2 , Xin Chen 1
1
Cancer Biology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, HI 96817, USA.
2
The Queen’s Medical Center, Honolulu, Hawaii, HI 96817, USA.
Correspondence to: Dr. Sandi Kwee, Cancer Biology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI
96817, USA. E-mail:kwee@hawaii.edu

How to cite this article: Kwee S, Chen X. Immunotherapy biomarkers for HCC: contemporary challenges and emerging
opportunities. Hepatoma Res 2022;8:32. https://dx.doi.org/10.20517/2394-5079.2022.58

Received: 10 Aug 2022 Accepted: 24 Aug 2022 Published: 29 Aug 2022

Academic Editors: Guang-Wen Cao, Giuliano Ramadori Copy Editor: Haixia Wang Production Editor: Haixia Wang

Clinical management of advanced unresectable HCC has indelibly changed with the advent of immune
checkpoint inhibitor (ICI) antibody therapy. The CheckMate-040 multi-cohort trial first demonstrated the
effectiveness of an anti-PD1 antibody (nivolumab) in patients with clinically advanced HCC previously
treated with sorafenib, reporting an approximately 20% overall objective response rate in such patients .
[1]
[2]
Another anti-PD1 agent, pembrolizumab, demonstrated similar response rates in its phase 2 trial , and
both agents subsequently received accelerated regulatory approval for second-line systemic treatment of
HCC. The CheckMate-040 trial later showed up to a 32% objective response rate in patients treated with
nivolumab plus ipilimumab (an antibody targeting CTLA-4), leading to approval of this combination
regimen for second-line therapy . With regards to first-line treatment of locally advanced or metastatic
[3]
and/or unresectable HCC, the IMbrave150 phase 3 randomized trial associated the combination of
bevacizumab plus atezolizumab (an anti-PD-L1 antibody) with improved overall survival over first-line
sorafenib, with an objective response rate of 30% (95%CI: 25%-35%) and median duration of response of
[4]
18.1 months based on a recent extended efficacy and safety analysis of the trial . Although remarkable for
the setting of advanced HCC, these findings congruously show that most patients eligible to receive ICI
therapy will not experience an objective benefit and that predictive biomarkers of treatment response will be
necessary to optimize the risk-benefit ratio of immunotherapy treatment in this setting.

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
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