Advances in Advanced Liver Cancer Treatment – Updated ASCO Guideline

Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide and is particularly difficult to treat at advanced stages. Historically, HCC treatment relied mainly on chemotherapy, but this approach was far from ideal because of limited effectiveness and significant side effects. Over the years, scientists and clinical researchers sought more effective and less toxic treatments. This effort led to the development of innovative approaches such as immunotherapies and targeted therapies.

Today, advanced HCC treatment focuses on targeted therapies combined with immunotherapy , particularly oral tyrosine kinase inhibitors (TKIs). These strategies have the potential to slow disease progression and extend overall survival while substantially improving patients' quality of life.

Worldwide, treatment guidelines published by the American Society of Clinical Oncology (ASCO) are recognized as critically important and widely accepted guidance for cancer treatment. ASCO's updated guideline on systemic therapy for advanced HCC marks a turning point in treatment practice. By providing comprehensive recommendations for first-, second-, and third-line treatment, it strongly emphasizes the central role of immunotherapy and targeted therapies in HCC treatment.

ASCO Updates for Advanced HCC Treatment

ASCO has updated its guidelines on the use of systemic therapy for advanced hepatocellular carcinoma (HCC).

First-Line Treatment

For patients with advanced HCC, Child-Pugh class A, and an ECOG performance status score of 0 or 1 , recommended first-line treatment is atezolizumab plus bevacizumab or durvalumab plus tremelimumab . This is a strong recommendation based on moderate- to high-quality evidence.

Patients with contraindications to atezolizumab plus bevacizumab or durvalumab plus tremelimumab may receive sorafenib, lenvatinib, or durvalumab as alternatives. This is also a strong recommendation based on moderate-quality evidence.

Second-Line Treatment

For patients with advanced HCC, Child-Pugh class A, and good performance status, second-line treatment recommendations vary according to the first-line treatment received.

For patients who received atezolizumab + bevacizumab first line, any of the following is recommended as second-line treatment:

• A tyrosine kinase inhibitor (TKI), such as sorafenib, lenvatinib, or cabozantinib, or ramucirumab (a weak recommendation based on low-quality evidence)
• Nivolumab + ipilimumab (based on data from case series)
• Durvalumab + tremelimumab. (There are no data supporting this recommendation.)

If durvalumab + tremelimumab was given first line, a TKI is recommended as second-line treatment (a weak recommendation based on low-quality evidence). Atezolizumab + bevacizumab may also be considered, although there are no data supporting this recommendation.

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Third-Line Treatment and Child-Pugh Class B HCC

For third-line treatment, patients with Child-Pugh class A disease and good performance status may receive any of the agents listed above that does not have the same mechanism of action as their previous treatments (a weak recommendation based on low-quality evidence).

For patients with Child-Pugh class B disease and good performance status, health care providers should consider underlying liver function, bleeding risk, portal hypertension, extent of extrahepatic spread, tumor burden, and major vascular invasion. Limited data suggest that regimens typically used for Child-Pugh class A disease may benefit previously untreated patients with Child-Pugh class B cirrhosis (a weak recommendation based on low-quality evidence).

These updates are critically important in advanced HCC treatment and expand the available options. Health professionals have an opportunity to optimize outcomes by tailoring these new guidelines to patients' individual needs.