ASCO Announces New Advanced Liver Cancer Guidelines

New guidelines from the American Society of Clinical Oncology were released to address the treatment of advanced hepatocellular carcinoma (HCC).

An unprecedented number of new agents have been approved for systemic therapy of HCC in recent years, which led to a call for a revision of guidelines.

Prior to this influx of new therapies, there were no new treatments approved for HCC since the approval of sorafenib in 2005. In particular, the new guidelines include a recommendation for the use of a combination of the immunotherapy atezolizumab and the antiangiogenic agent bevacizumab for the first-line treatment of HCC.

To develop an evidence-based clinical practice guideline for advanced HCC, ASCO convened an expert panel. The panel conducted a systematic review of phase 3 randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and developed recommendations based on the findings.

Nine phase 3 randomized controlled trials met the inclusion criteria.

The resulting ASCO guidelines were published in the Journal of Clinical Oncology

Highlights

“The major highlight of the guidelines is a recommendation for the combination of atezolizumab and bevacizumab for first-line therapy of most patients with advanced HCC. This combination was the first combination treatment using immunotherapy approved in this space,” said coauthor Muhammad Shaalan Beg, MD, of UT Southwestern Medical Center, Dallas.

“Multiple drug approvals for HCC mark a significant advancement in this disease which is historically considered recalcitrant. However, clinicians may have trouble selecting the right drug for the right patient at the right time in their disease course. The ASCO guidelines are geared towards providing clear guidance on how to incorporate these agents for patients with advanced HCC.”

The new guidelines state that where there are contraindications to atezolizumab/bevacizumab, tyrosine kinase inhibitors (TKIs) sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC. Following first-line treatment with atezolizumab/bevacizumab, and until better data are available, second-line therapy with a TKI may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with alpha-fetoprotein ≥ 400 ng/mL), or atezolizumab/bevacizumab where patients did not have access to this option as first-line therapy.

Future Directions

The guidelines also look to future directions in advanced HCC. “We will look at sequencing immuno-oncology and TKI agents. We await the results of key trials using immuno-oncology/TKI combinations and dual immuno-oncology combinations,” said Beg. “Molecular targeted treatments remind clinicians and researchers of the need for adequate tissue-based diagnosis of HCC.”

The guidelines note that clinicians need to take into account health disparities and cost considerations with HCC therapies. “HCC is a disease that disproportionately affects economically disadvantaged groups and underrepresented minority groups. The combination of atezolizumab/bevacizumab, approved for first-line therapy, may be a very high-cost treatment. Treatment will be limited to those with adequate health coverage/insurance. These factors can further increase the disparities in outcomes of HCC,” said Beg. He noted that risk factors of HCC include hepatitis C, alcohol-related liver disease, and cirrhosis.

“Health systems, insurance agencies, and clinicians need to pay particular attention to allow access of these drugs to patients. Early diagnosis and initiation of treatment are keys so that patients can be treated when their liver function is appropriate to enable good cancer outcomes,” added Beg.

Ongoing Trials

Daneng Li, MD, of City of Hope, in Duarte, Calif., commented: “Patients who are eligible for the combination of atezolizumab and bevacizumab should be treated in the first line. This is the new standard of care as first-line treatment for advanced HCC. If there are contraindications, then either sorafenib or lenvatinib are an option for first-line treatment. This is very consistent with what practicing clinicians are starting to recognize.” He noted that there are no large phase 3 second-line trials of a TKI after lenvatinib or a frontline combination of atezolizumab/bevacizumab.

“The new guidelines are consistent with the recent rapid advances in the landscape for the treatment of advanced HCC. They can help community practitioners who might not see as many cases of advanced HCC keep up to date,” said Li.

“Research is rapidly progressing. Currently there are at least four major first-line combination trials with dual immuno-oncoIogy therapies or immuno-oncology plus a TKI. If any of those trials are positive, the guidelines will need to be revised immediately.”

Li added: “With multiple options available, we may be able to select the ideal combination for the individual patient. We now have good options for a disease that traditionally had a poor prognosis. I believe we are at a point of making more breakthroughs. Innovative combinations really allow these patients to live longer and better lives.”

Beg reported consulting and advising for Ipsen, Boston Biomedical, Array BioPharma, and AstraZeneca/MedImmune, and receiving research funding from numerous sources in industry. Li reported grant/research support to his institution from Boston Immunotherapeutics and consulting with Ipsen, Eisai, Exelixis, Roche-Genentech, and Merck.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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