ASCO Updates Advanced HCC Treatment Guideline

John D. Gordan, MD, PhD

The American Society of Clinical Oncology (ASCO) has updated the 2020 guideline regarding the use of systemic therapy for the treatment of patients with advanced hepatocellular carcinoma (HCC).¹

The updated guideline supports the use of atezolizumab (Tecentriq) plus bevacizumab (Avastin) or durvalumab (Imfinzi) plus tremelimumab (Imjudo) for the frontline treatment of patients with advanced HCC. Patients must also have Child-Pugh class A liver disease and an ECOG performance status of 1 or less. The evidence quality for this recommendation was moderate to high and the strength of the recommendation was strong. The ASCO expert panel noted that the risk of bleeding and thrombosis with bevacizumab should be considered when weighing the use of the 2 regimens.

The panel also added that in the event of contraindications to either combination, sorafenib (Nexavar), lenvatinib (Lenvima), or durvalumab (Imfinzi) could be offered as frontline treatment for patients with advanced HCC and Child-Pugh class A disease and an ECOG performance status of 1 or less. The evidence quality for this recommendation was moderate and it was deemed a strong recommendation.

“This guideline integrates several important new therapeutic advances into the treatment of these kinds of cancers, and I think without some degree of information about that there would be an open question about how to use them,” John D. Gordan, MD, PhD, an associate professor of medicine at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center and panel co-chair, said. “It also addresses the use of CTLA-4/PD-1 inhibitor combinations, which were not addressed [in the prior guideline].”2

To update the 2020 guideline in advanced HCC, ASCO convened a multidisciplinary panel, including a patient representative and an ASCO guidelines staff member. The prior guideline was based on findings from a systematic literature search of phase 3 clinical trials published between January 1, 2007, and May 15, 2020. The search was updated to include trials that had been published up to October 5, 2023. The studies needed to enroll patients with unresectable advanced HCC, including those who were not candidates for surgery or liver-directed treatment. The panel considered any targeted agents or immunotherapy agents alone or in combination with other therapies that were available in the United States.1

Eight phase 3 studies from the 2020 version of the guideline were retained for inclusion in the evidence base for the 2023 update. Additionally, 10 new clinical trials were added to the evidence base, consisting of 7 examining frontline therapies, 2 of second-line treatments, and 1 that enrolled patients who were treatment naive or initially recurrent.

Additional recommendations from the panel endorsed second-line treatment with a TKI or ramucirumab (Cyramza) following treatment with atezolizumab plus bevacizumab; this recommendation had a low quality of evidence and the strength of the recommendation was weak. Additionally, the panel listed TKIs as second-line therapy following treatment with durvalumab plus tremelimumab; this recommendation also had a low quality of evidence and a weak strength.

After frontline treatment with sorafenib or lenvatinib and second-line therapy with another TKI, ramucirumab, durvalumab, or nivolumab (Opdivo) plus ipilimumab (Yervoy) could be recommended for appropriate patients. Atezolizumab plus bevacizumab or durvalumab plus tremelimumab could also be considered for patients who may not have had access to these therapies in the first-line setting, and do not have contraindications to these combinations. The evidence quality of this recommendation was low to moderate and the strength was weak.

In terms of Child-Pugh score, the panel recommended that third-line therapy could be considered in Child-Pugh A patients with good performance status using one of the suggested aforementioned agents with a different mechanism of action than the previously given treatment; this recommendation was weak with a low quality of evidence. Finally, the panel endorsed a cautious approach to systemic therapy in patients who are Child-Pugh class B with good performance status, emphasizing shared decision-making with patients. This recommendation had a very low quality of evidence and a weak strength.

“I think most oncologists are already aware of many of the studies summarized in this guideline, but I hope this update helps them rapidly select the appropriate therapy for the individual patient, based on their prior treatment, comorbidities, and preferences,” Michal G. Rose, MD, a professor at Yale School of Medicine in New Haven, Connecticut, and the director of the Veterans Affairs Comprehensive Cancer Center at VA Connecticut Health Care System, and a panel co-chair, said. “With the rapid expansion of data in all fields of cancer care, it is hard for the practicing oncologist to stay abreast of all these developments.”²

References

• Gordan JD, Kennedy EB, Abou-Alfa GK, et al. Systemic therapy for advanced hepatocellular carcinoma: ASCO guideline update J Clin Oncol. Published online March 19, 2024. doi:10.1200/JCO.23.02745
• Guideline update seeks to aid clinicians in the selection of systemic treatments for advanced hepatocellular carcinoma. ASCO Daily News. March 20, 2024. Accessed April 26, 2024. https://dailynews.ascopubs.org/do/guideline-update-seeks-aid-clinicians-selection-systemic-treatments-advanced