Abstract
Simple SummaryFor years, the systemic therapies sorafenib and lenvatinib have represented standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). The recent approval of atezolizumab in combination with bevacizumab heralded the arrival of immunotherapy for first-line treatment of advanced HCC, and the field is growing, with other combination immunotherapies under investigation. Focusing on the Asia–Pacific region, where drug availability and reimbursement systems differ widely, this article reviews the evolving treatment landscape and summarises the authors’ expert opinion on therapeutic decision-making to optimise outcomes in advanced HCC.Hepatocellular carcinoma (HCC) is the fourth most common driver of cancer-related death globally, with an estimated 72% of cases in Asia. For more than a decade, first-line systemic treatments for advanced or unresectable HCC were limited to the multi-targeted kinase inhibitors sorafenib and, more recently, lenvatinib. Now, treatment options have expanded to include immunotherapy, as exemplified by the immune checkpoint inhibitor (ICI) atezolizumab combined with the antiangiogenic agent bevacizumab. Additional combinations of ICIs with kinase inhibitors, other ICIs, or antiangiogenic agents are under investigation, further supporting the new era of immunotherapy for first-line treatment of advanced or unresectable HCC. We describe this evolving landscape and provide expert opinion on therapeutic best practices in the Asia–Pacific region, where different costs of, and patient access to, treatment are a challenge. With the combination of atezolizumab plus bevacizumab likely to become the clinical standard of care, optimising treatment sequence and ensuring patient access to newer therapies remain priorities. Cost containment and treatment sequencing may be facilitated by characterisation of predictive positive and negative biomarkers. With these considerations in mind, this review and expert opinion focused on advanced HCC in the Asia–Pacific region offers perspectives of multiple stakeholders, including physicians, payer systems, and patients.
Highlights
Liver cancer is a common cancer in multiple geographically diverse regions, especially East Asia and Southeast Asia [1]
For ease of comparison and discussion of treatment approaches, we refer to the Barcelona Clinic Liver Cancer (BCLC) system, which classifies patients according to tumour status, liver function (by Child– Pugh (CP) category), and performance status (PS) as defined by the Eastern Cooperative Oncology Group (ECOG) [6]
On the basis of the patient population enrolled in the IMbrave150 study, it appears that for patients with advanced Hepatocellular carcinoma (HCC) for whom immunotherapy is not appropriate, such as those at higher risk, sorafenib and lenvatinib remain treatments of choice until further clinical trial and realworld evidence is obtained for immunotherapy approaches
Summary
Liver cancer is a common cancer in multiple geographically diverse regions, especially East Asia (an area that includes China, Japan, South Korea, and Taiwan) and Southeast Asia (which includes Singapore) [1]. In the phase 3 study of first-line combination therapy with the programmed cell-death 1 ligand 1 (PDL1) inhibitor atezolizumab and the vascular endothelial growth factor (VEGF) inhibitor bevacizumab versus standard-of-care sorafenib for advanced HCC (IMbrave150 trial, NCT03434379), treatment with the novel combination resulted in significantly better outcomes than were achieved with sorafenib [9]. Such an expansion of options brings with it the challenges of treatment selection and sequence. In light of positive results of combination immunotherapy from the IMbrave150 trial, we, as representatives of several key constituents of the Asia–Pacific region, seek to describe the current and evolving treatment landscapes in advanced HCC with the aim of providing expert opinion on best practices for treatment of advanced HCC in our region, with special focus on China, Japan, Singapore, South Korea, and Taiwan
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