| Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the third leading cause of cancer-related death worldwide. The majority of patients present with advanced-stage, unresectable HCC (uHCC), amenable only for local and systemic therapies. Notably, recent advances in immunotherapy and targeted therapies have led to the approval of many immune checkpoint inhibitors (ICIs) and anti-angiogenesis therapies. Numerous ongoing clinical trials are assessing combined ICIs and targeted therapies in advanced and earlier stages of HCC, either alone or in combination with local therapies. Furthermore, neoadjuvant and adjuvant systemic therapies are being investigated for their potential to reduce recurrence after resection and improve overall survival. This presentation will identify various translational research and clinical trials showing impressive preliminary signals of disease control in uHCC and pathologic complete response in resectable HCC. Heterogeneity in patient population, trial design, therapies used, patient selection, and a scarcity of randomized phase III trials necessitate the cautious implementation of these treatment strategies. Therefore, future research is required to identify predictive biomarkers and optimize patients' selection and the timing and type of therapeutic combinations to personalize future clinical trials approaches in early- and advanced-stage HCC. |
