Page 22 - 台灣肝癌醫學冬季會手冊-1222-V3_Neat

ICI monotherapy or combination: real-world experience

Chi-Jung Wu, MD.

Division of Gastroenterology & Hepatology, Taipei Veterans General Hospital;

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of
cancer related death worldwide that constitutes a major global health problem. Despite improvement
in surveillance and hepatitis B vaccination, hepatitis C treatment, a large number of patients still

present with unresectable, advanced-stage disease and require systemic therapy. Recently, several
promsing results from the phase 2/3 trials of first or second line settings enable HCC patients access
to more treatment options. Manipulation of immune checkpoints by targeted antibodies against
programmed cell death-1 (PD-1), or programmed death-ligand 1 (PD-L1) axis, have recently

emerged as an effective anticancer strategy for many types of cancers, including HCC.
Nivolumab is the first FDA-approved immune checkpoint inhibitor for HCC, yielded an objective
response rate (ORR) of 14% and 9-month survival rate of 74% in second line setting.
Pembrolizumab, another antibody against PD1, showed a similar response rate as nivolumab in phase

2 (Keynote 224) and phase 3 (Keynote 240) trials of HCC patients for second line treatment. The
real-world experience of immunotherapy for unresectable HCC from Taiwan showed an ORR of
24.4%. A 10-10 rule of early AFP response can predict objective response and survival to immune
checkpoint inhibitor (ICI) treatment in unresectable HCC. ALBI grade and Child-Pugh class

determines survival by ICI treatment. Nivolumab had tried to expand its role in the first line setting,
but it did not reach statistically difference to sorafenib in a phase 3 CheckMate 459 trial. Recently,
combination treatment of atezolizumab plus bevacizumab in a phase 3 IMbrave 150 trial has showed
an ORR of 27%, and overall survival of not yet reached in first line setting. Pembrolizumab plus

lenvatinib also confirmed ORRs was 36.0% per RECIST v1.1, and median overall survival was 22
months in phase 1b Keynote 524 trial for first line systemic treatment for HCC. Nivolumab plus
ipilimumab showed an ORR of 32% and median OS of 22.8 months in second line setting.
Combination treatment will be a promising strategy in the treatment of advanced HCC in the future.