Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC incidence has tripled in the US since 1980. New treatment options have become available in recent years for patients who aren’t good candidates for surgical interventions.

The American Gastroenterological Association (AGA) has conducted a thorough literature review and recently released clinical practice guidelines on the use of systemic therapy to treat patients with HCC that were published in Gastroenterology.

Su GL, Altayar O, O’Shea R, et al. AGA clinical practice guideline on systemic therapy for hepatocellular carcinoma. Gastroenterology. 2022;162(3):920–934.

 

 

Target audience

However, the guidance also highlights using a multidisciplinary team that includes radiologists and oncologists to come up with the best treatment plan for each patient.

“Deciding the best treatment for your liver cancer patient is not a one-doctor decision,” said lead author Grace L. Su, MD in a press release.

AGA recommends shared decision-making approach for treatment of hepatocellular carcinoma (HCC). EurekAlert. February 22, 2022.

“Our hope is that this new guideline empowers GI doctors to build relationships with multidisciplinary providers, such as oncologists, that will ultimately determine the best individualized treatment for their patients.”

 

 

Key recommendations

The AGA put together a multidisciplinary group that agreed on 11 recommendations for use of systemic therapy in patients with HCC who aren’t eligible for resection or locoregional therapy (LRT).

The recommendations also provide clinical practice guidelines for patients with metastatic disease, preserved liver function, or poor liver function, as well as those receiving systemic therapy as adjuvant therapy.

MDLinx summarizes specific recommendations from the AGA guidance below.

 

First-line therapies for HCC in patients with preserved liver function

For HCC patients with preserved liver function who aren’t eligible for LRT or resection or those who have metastatic disease, the AGA recommends the combination of atezolizumab+bevacizumab over sorafenib. The AGA based this on one study which demonstrated that the combination of atezolizumab (an immune checkpoint inhibitor) and bevacizumab (an anti-angiogenic agent) was superior to sorafenib.

However, the guidance acknowledges that bevacizumab poses a known risk of gastrointestinal bleeding and all study participants who received the combination of bevacizumab and atezolizumab had to have an endoscopic evaluation. Patients with esophageal varices were treated before receiving bevacizumab.

 

Second-line treatment options for patients with preserved liver function

In patients who have disease progression or who are intolerant to first-line therapy, the AGA has made the following recommendations:

1. For patients with HCC with preserved liver function who aren’t eligible for LRT or resection, or those with metastatic disease who’ve had disease progression while taking sorafenib, the AGA recommends cabozantinib, pembrolizumab, or regorafenib over no systemic therapy.

2. For patients with HCC with preserved liver function and α-fetoprotein (AFP) > 400 ng/mL who aren’t eligible for LRT or resection, or those with metastatic disease who’ve had progression of disease on sorafenib, the AGA recommends using ramucirumab over no systemic therapy.

 

Systemic treatment options for HCC patients with impaired liver function

 

The AGA cautions against routine use of sorafenib in HCC patients with poor liver function who aren’t eligible for LRT or resection, or those with metastatic disease. While most studies in patients with advanced HCC exclude patients with poor liver function, the AGA found one study in which patients with impaired liver function were randomly assigned to receive either oral sorafenib or the best supportive care.

While the study showed an improvement in mortality, the median overall survival was poor, with 4 months in the sorafenib group and 3.5 months in the best supportive group. However, the AGA notes that this study was flawed in that there was a lack of blinding and inadequate allocation concealment, leading to a high risk of bias.

 

Systemic therapy for HCC as adjuvant therapy

The AGA makes similar recommendations for HCC patients undergoing local ablation, as well as for patients undergoing transarterial chemoembolization (TACE) LRT. In addition, for those undergoing TACE LET, the AGE also recommends against bevacizumab adjuvant therapy.