Advances in targeted therapy combined with immunotherapy for advanced hepatocellular carcinoma

The IMbrave 150 study opened the door of immunotherapy combined with targeted therapy, and then the data of ORIENTAL-32, a Phase Ⅲ clinical trial for Chinese patients, was released, which confirmed the efficacy of immunotherapy combined with targeted therapy, especially significant survival benefits in Chinese patients. At present, there are many ongoing studies on PD-1/PD-L1 inhibitors combined with small-molecule tyrosine kinase inhibitors, and their corresponding early data provide a considerable objective response rate, which provides an opportunity for conversion therapy/sequential therapy for hepatocellular carcinoma in different stages and courses, as well as a basis for further exploration of neoadjuvant/adjuvant therapy. Combined immunotherapy has entered the era of version 3.0, in which reasonable local therapy can be implemented at different stages in combination with targeted drugs. However, there are still no accurate predictive indicators for efficacy, and it requires comprehensive consideration of the features such as the natural course of the disease, clinicopathological parameters, genomics, and radiomics. Compared with single-drug immunotherapy or single-drug targeted therapy, immunotherapy combined with targeted therapy had a relatively complex spectrum of adverse reactions and difficult identification of correlation, and whole-process management, comprehensive judgment, and timely treatment should be performed within the framework of multidisciplinary team.