Editor’s Note:
Early-stage liver cancer can be cured with radical surgery. However, tumor recurrence remains the primary challenge affecting patients’ long-term survival. Currently, the five-year recurrence rate for early-stage liver cancer post-surgery is about 60%. Addressing this challenge and improving long-term survival for these patients is a pressing clinical issue. From July 6th to 8th, 2023, the 13th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2023) was held grandly in Seoul, South Korea. A special session on “Unmet Clinical Needs and Research Directions” was set up, inviting several internationally renowned liver cancer scholars for an in-depth discussion. During this, Dr. Linda Wong from the University of Hawaii shared her insights on the promising vision of adjuvant therapies, such as systemic therapy and TACE, for the cure of early-stage liver cancer.
Hepatology Digest: Could you elaborate on the recent research developments to further enhance long-term survival in early-stage liver cancer patients?
Dr. Wong: Currently, the five-year survival rate after curative liver cancer surgery is about 50%, or even as high as 60%. Yet, we aim to improve this further. Recent clinical studies are exploring the potential application of systemic treatments and TACE as adjuvant therapies to reduce post-operative liver cancer recurrence.
For instance, the latest data from the IMbrave050 study presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting revealed statistically significant improvements in recurrence-free survival (RFS) with the combination of PD-L1 inhibitor Atezolizumab and Bevacizumab (abbreviated as “T+A”) in HCC patients with high recurrence risk post-curative resection or ablation.
This open-label Phase III trial involved HCC patients who underwent curative resection or ablation, randomized 1:1 to either the “T+A” adjuvant treatment group or a control group. The “T+A” regimen lasted approximately one year (17 cycles). As of September 21, 2022, with a median follow-up time of 17.4 months, the Independent Review Committee’s (IRF) RFS data showed an HR of 0.72, indicating a significant 28% reduction in disease recurrence, distant metastasis, or death risk for HCC patients treated with the “T+A” regimen.
Ongoing studies are evaluating other immune checkpoint inhibitors alone or in combination with targeted drugs as adjuvant postoperative therapies for liver cancer. For example, a study showed a 1-year RFS of 78.6% and a median RFS of 26.3 months in liver cancer patients with moderate to high recurrence risk treated with Nivolumab after curative resection or ablation.
Moreover, multiple studies combining targeted drugs with local treatments are underway. One prospective cohort study demonstrated a median disease-free survival (DFS) of 17 months in liver cancer patients with high recurrence risk treated with Lenvatinib combined with TACE, compared to a median DFS of 9 months for the TACE control group (HR=0.6, 95%CI: 0.4~1.0, P=0.0228).
In summary, we anticipate these clinical research results to be further validated. We believe adjuvant therapy holds considerable promise in redefining the treatment paradigm for early-stage liver cancer.
Hepatology Digest: Where else can we explore more in early-stage liver cancer treatment?
Dr. Wong: Beyond interventions, targeted treatments, and immunotherapies, post-operative adjuvant treatments also encompass treatments targeting underlying liver conditions like chronic hepatitis B and C and treatments targeting moderate to high recurrence risk factors. Thus, it’s imperative to continue anti-HBV treatments post-surgery for liver cancer patients with a hepatitis B background, and standardized antiviral treatments for those with active hepatitis C. Therefore, more efforts are needed in treating viral hepatitis to proactively prevent liver cancer.
In early-stage liver cancer treatment, I believe another crucial direction is liver cancer prevention. We must ensure universal hepatitis B vaccination, which requires more robust efforts, and continue research into a hepatitis C vaccine. Additionally, studies suggest early use of aspirin, statins, and metformin may have a liver cancer prevention effect. We need further research to understand their underlying mechanisms. These are directions ripe for exploration.
Hepatology Digest: Could you share some of your team’s major research achievements in recent years and their clinical significance?
Dr. Wong: Over the past nearly three decades, I’ve been engaged in clinical research related to chronic liver diseases and liver cancer. I believe that a deeper understanding of these diseases will enable earlier detection, improved treatments, and ultimately successful prevention of liver cancer. Viral hepatitis is a primary cause of liver cancer, and Hawaii, where I work, is among the regions in the US with the highest incidence of liver cancer. This region has a high prevalence of viral hepatitis, with a population mainly comprising immigrants from Asia and the Pacific Islands, where hepatitis B is endemic. Therefore, there are significant racial disparities in treatments for viral hepatitis and liver cancer. In recent years, our team’s clinical research has primarily focused on racial disparities in liver cancer. We aim to identify which ethnic groups in Hawaii are more prone to liver cancer and try to find the associated molecular mechanisms. This will aid us in identifying molecular intervention points for liver cancer and advance personalized treatments.
*This article combines expert interviews and reports.
