New Guidelines Clarify Use of Systemic Therapy in Advanced HCC

Liam Davenport

February 24, 2022

Only patients with advanced hepatocellular carcinoma (HCC) and preserved liver function should receive systemic therapies, according to new clinical practice guidelines from the American Gastroenterological Association.

That is one major takeaway from an AGA panel of experts who provided 11 total recommendations for the management of HCC, focusing largely on first- and second-line options in patients with advanced disease who are not eligible for locoregional therapy or resection.

The aim of the guidelines, published online February 21 in Gastroenterology, was to provide a "critical assessment" of the existing evidence on the array of new systemic options that have emerged for patients with HCC in recent years.

Lead author Grace L. Su, MD, from the University of Michigan Health System, Ann Arbor, also hopes the guidelines highlight the importance of involving multidisciplinary teams — including gastroenterologists, hepatologists, radiologists, and oncologists — in the decision-making process.

"Deciding the best treatment for your liver cancer patient is not a one-doctor decision,” she said in a press release. "Our hope is that this new guideline empowers gastrointestinal doctors to build relationships with multidisciplinary providers, such as oncologists, that will ultimately determine the best individualized treatment for their patients."

A multidisciplinary group reviewed the evidence on systemic therapies in patients with advanced-stage HCC and developed a series of recommendations covering a range of clinical scenarios across the disease spectrum.

Here are some highlights from the practice guidelines.

In the first-line setting, Su and colleagues recommend atezolizumab (Tecentriq) plus bevacizumab (Avastin) over the previous therapeutic standby, sorafenib (Nexavar), in patients with advanced HCC and preserved liver function. However, for those who are not candidates for the combination therapy, approved in 2020, the AGA panel suggests either lenvatinib (Lenvima) or sorafenib in the first-line over no systemic therapy.

For patients who progress after first-line therapy, recommended second-line therapies include cabozantinib (Cometriq), pembrolizumab (Keytruda), ramucirumab (Cyramza), and regorafenib (Stivarga), with caveats listed for each option. For instance, "patients who place a higher value on adverse effects associated with pembrolizumab and lower value on the reduction in mortality (3.3 months) may reasonably decline pembrolizumab," the authors write.

The authors also acknowledge that "no high-quality direct comparative evidence" exists for the use of atezolizumab plus bevacizumab, sorafenib, or lenvatinib in the second-line setting. "However, patients who place a high value on the uncertain benefit of these agents as second-line therapies, and a low value on their adverse events, may reasonably" choose them.

For patients with poor liver function, the panel recommends against routine use of sorafenib, but include the caveat that patients "who place a higher value on the uncertain reduction in mortality and lower value on the harms, may reasonably select to use sorafenib."

For patients with early HCC, defined as stage 0 and A, the guideline recommends that candidates for ablation, resection, or transplant receive curative surgery, rather than systematic therapies.

For those with intermediate, or stage B, disease, the panel says patients should receive transarterial chemoembolization as first-line therapy and recommend against the use of adjuvant sorafenib.

And for those with terminal disease, systemic therapy is also not recommended. Here, the guideline advises transplant or best supportive care.

The authors note that the recommendations, which were all labeled "conditional," generally align with those from the American Society of Clinical Oncology and the National Comprehensive Cancer Network, with several differences. For instance, the American Society of Clinical Oncology guidelines suggest using atezolizumab plus bevacizumab or nivolumab (Opdivo) as second-line therapy in patients who fail sorafenib or lenvatinib in the first-line setting — options the panel "identified as a knowledge gap due to lack of [randomized controlled trials]."

Ultimately, however, the authors stress that "decisions for treatment selection need to weigh patient preferences as well as risks and benefits."

Development of the guideline was funded by the American Gastroenterological Association Institute without any additional outside funding. The authors declared no relevant financial relationships.

Gastroenterology. Published online February 21, 2022. Full text

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