Editor’s Note: The Phase III EMERALD-1 study has shown that for patients with unresectable intermediate to advanced hepatocellular carcinoma (HCC), the combination of durvalumab, bevacizumab, and transarterial chemoembolization (TACE) significantly improves progression-free survival (PFS) compared to TACE alone. At the 2024 International Liver Cancer Association (ILCA) conference, Dr. Stephen L. Chan from the Faculty of Medicine at The Chinese University of Hong Kong presented a safety and efficacy analysis from the EMERALD-1 study, considering treatment timing and baseline liver function. In an interview with Oncology Frontier , he shared the latest insights from this analysis.

Oncology Frontier: In your presentation, you mentioned combining immune checkpoint inhibitors (ICIs) with transarterial treatments like TACE for BCLC Stage B liver cancer patients. What scientific hypothesis or prior research findings is this combination strategy based on?

Dr. Stephen L. Chan: This hypothesis is based on the idea that combining systemic therapy—such as durvalumab and bevacizumab—with TACE could create a synergistic effect with locoregional therapy to improve patient outcomes. This combination may activate the immune system while also delivering localized treatment directly to the tumor, potentially enhancing the overall treatment effect.

Oncology Frontier: Compared to single therapies, what are the specific advantages or improvements of this combination approach in terms of improving patient survival rates and extending progression-free survival?

Dr. Stephen L. Chan: This combination treatment has shown superior survival benefits over single therapies. Compared to the placebo plus TACE group, the experimental arm—including durvalumab, bevacizumab, and TACE—demonstrated significant improvements in progression-free survival. Additionally, it was associated with a higher response rate and an acceptable side effect profile, supporting the hypothesis that this immunotherapy-based systemic approach can work synergistically with TACE to improve outcomes for HCC patients.

Oncology Frontier: In the EMERALD-1 study, the treatment with durvalumab, bevacizumab, and TACE was divided into two treatment phases: the D-TACE (D-T) phase and the D-B (durvalumab and bevacizumab) phase. Could you elaborate on the safety profile of this regimen during these two distinct phases?

Dr. Stephen L. Chan: In the EMERALD-1 study, the first phase consists of 16 weeks of TACE combined with durvalumab. The second phase, known as the maintenance or systemic therapy phase, involves only durvalumab and bevacizumab. We assessed safety and adverse events across both phases. During the 16-week TACE phase, there was no significant difference in adverse events between the experimental and control arms. In the systemic therapy phase, however, we observed a slightly higher rate of Grade 3/4 adverse events in the experimental arm, though there were no treatment-related deaths. This slight increase in adverse events may be attributed to the longer duration of treatment in the durvalumab and bevacizumab arm compared to the placebo arm. Overall, we did not observe any significant safety signals, and the side effect profile was consistent with expectations.

Oncology Frontier: The study abstract mentions that, regardless of baseline ALBI (albumin-bilirubin) grade, the D+B+TACE group showed numerical improvements in both progression-free survival (PFS) and time-to-progression (TTP) compared to the PBO+TACE group. How do you think baseline liver function status specifically impacts the efficacy of the durvalumab, bevacizumab, and TACE combination therapy? What guidance does this finding offer for patient selection and treatment adjustments in clinical practice?

Dr. Stephen L. Chan: In our exploratory analysis, we evaluated the performance of the combination therapy—durvalumab, bevacizumab, and TACE—in patients with different baseline liver function statuses, specifically ALBI Grades 1 and 2. For both groups, we saw improvements in PFS and TTP in the experimental arm compared to the placebo arm, with similar hazard ratios. This suggests that patients derive benefit from the combination therapy regardless of their baseline liver function. This finding underscores the broad applicability of this treatment, supporting its use across different liver function statuses and helping clinicians make more inclusive treatment decisions.

Oncology Frontier: Based on the results of the EMERALD-1 study, what are your thoughts on the long-term application prospects of the durvalumab, bevacizumab, and TACE combination as a potential new standard treatment for unresectable HCC? What further research is needed to confirm its efficacy and safety, and to explore its potential for a broader patient population?

Dr. Stephen L. Chan: I think the EMERALD-1 study brings several key messages. First of all, it’s a positive study, showing improvement in progression-free survival, time-to-progression, and response rates, all with a reasonable toxicity profile. These results support the use of this combination therapy in clinical practice. While systemic therapy is traditionally used in advanced settings, we see potential for its application in intermediate-stage HCC as well, offering a more aggressive treatment option. This approach could even make some patients eligible for surgical intervention down the line. Future research should focus on further validating these findings in larger patient cohorts and exploring the possibility of integrating this combination therapy into earlier stages of HCC treatment.