Abstract
Although many approaches have been developed for the treatment of hepatocellular carcinoma (HCC) that has both high incidence and high mortality especially in Asian countries, the prognosis of HCC patients is still dismal. Immunotherapy, particularly immune checkpoint inhibitors show encouraging efficacy and have already been widely applied in clinic. However, in contrast to traditional therapies, immunotherapy brings many challenges when using in a real world, including biomarker discovery, response evaluation, adverse event treatment, etc. In this review, we proposed some important and intractable issues in current clinical practice regarding the strategy of immune checkpoint blockade, collected current evidence, and discuss the critical challenges and possible approaches to a bright future.
Highlights
Many treatment modalities including hepatic resection, liver transplantation, radiofrequency ablation, transcatheter arterial chemoembolization (TACE), and tyrosine kinase inhibitors have been widely used in clinical practice, the prognosis of hepatocellular carcinoma (HCC) is still dismal
In a cohort of East Asian patients with HCC, up to 23% patients who received PD-1 blockade were reported to suffer from hyperprogressive disease (HPD) [57]
Clinical observation revealed that some patients responded to immune checkpoint inhibitors (ICIs) with tumor shrinkage or stable disease that was consistent with Response Evaluation Criteria in Solid Tumors (RECIST) criteria; distinct immune-related patterns of response have been noted, including development of new lesions associated with edema and infiltration of immune cells and transient increase in the size of primary lesions [58]
Summary
Many treatment modalities including hepatic resection, liver transplantation, radiofrequency ablation, transcatheter arterial chemoembolization (TACE), and tyrosine kinase inhibitors have been widely used in clinical practice, the prognosis of hepatocellular carcinoma (HCC) is still dismal. Anti-tumoral immunotherapies especially immune checkpoint inhibitors (ICIs) show encouraging efficacy and shed light on future treatment of HCC. Data for the clinical efficacy of ICIs in HCC were mostly from the CheckMate 040 and KEYNOTE-224 trials (both trials testing anti-PD-1 antibodies), which showed an objective response rate of 15–20% as a second-line setting [2, 3]. ICIs have been frequently used for HCC treatment in the real world, no phase III trial has been reported. At least 9 phase III trials are currently ongoing, investigating the efficacy of ICIs in various clinical scenarios (Table 1). In real world some late-stage HCC patients received ICIs beyond this indication, and various clinical trials investigating ICIs as a first-line therapy or neoadjuvant therapy are ongoing. These issues are closely related to interpretation of the clinical trials, and warranted a deep discussion, which will improve the clinical management and refine the design of future clinical trials
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