Internal medicine

Systemic therapy

Regorafenib

Lenvatinib

Immunotherapy

Hepatocellular carcinoma

Colorectal cancer

Cancer

Oncology

Intensive care medicine

Atezolizumab

Combination therapy

Chemotherapy

Durvalumab

Bevacizumab

Targeted therapy

Sorafenib

Ramucirumab

Nivolumab

Breast cancer

Clinical trial

Medicine

Nature Reviews Gastroenterology & Hepatology

Hepatocellular carcinoma (HCC) is one of the most common solid malignancies worldwide. A large proportion of patients with HCC are diagnosed at advanced stages and are only amenable to systemic therapies. We have witnessed the evolution of systemic therapies from single-agent targeted therapy (sorafenib and lenvatinib) to the combination of a checkpoint inhibitor plus targeted therapy (atezolizumab plus bevacizumab therapy). Despite remarkable advances, only a small subset of patients can obtain durable clinical benefit, and therefore substantial therapeutic challenges remain. In the past few years, emerging systemic therapies, including new molecular-targeted monotherapies (for example, donafenib), new immuno-oncology monotherapies (for example, durvalumab) and new combination therapies (for example, durvalumab plus tremelimumab), have shown encouraging results in clinical trials. In addition, many novel therapeutic approaches with the potential to offer improved treatment effects in patients with advanced HCC, such as sequential combination targeted therapy and next-generation adoptive cell therapy, have also been proposed and developed. In this Review, we summarize the latest clinical advances in the treatment of advanced HCC and discuss future perspectives that might inform the development of more effective therapeutics for advanced HCC. This Review discusses the current and emerging therapeutic landscape for treatment of advanced hepatocellular carcinoma, including molecular-targeted monotherapies, immuno-oncology monotherapies, combination therapies and novel therapeutic approaches.

Evolving therapeutic landscape of advanced hepatocellular carcinoma