| 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, including multikinase inhibitors and immunotherapy. 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. In Taiwan, all the currently FDA approved TKI and immunotherapy for HCC are available in market, but only sorafenib, lenvatinib as the first line, and regorafenib for sorafenib failed are reimbursed by Taiwan National Health Insurance. 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. From May 2019 to March 2020, nivolumab had been once covered by Taiwan NHI, with the ORR of 16.1% and DCR of 21.7%. This reimbursement was terminated since the first April, 2020. 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 (Cancers (Basel). 2020;12(1):182) 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. Lenvatinib is enrolled in Taiwan NHI since Jan 2020 with rapidly growing recently. 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; Nivolumab plus ipilimumab also showed encouraging results in the first line and the second line settings. Combination treatment will be a promising strategy in the treatment of advanced HCC and is ongoing in Taiwan. |
