According to results from the phase 3 EMERALD-1 study, the combination of transarterial chemoembolization (TACE) and durvalumab, followed by durvalumab and bevacizumab, improved the progression-free survival (PFS) among patients with hepatocellular carcinoma, compared with TACE alone.

These results were presented by Riccardo Lencioni, MD, Pisa University School of Medicine, Pisa, Italy, at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium on Saturday, January 20, 2024, in San Francisco, California.

While TACE is the standard of care for patients with embolization-eligible unresectable hepatocellular carcinoma, most patients progress within 1 year. Dr Lencioni explained, “Research in other studies suggested that TACE would work well with two other types of anticancer therapy: immunotherapy, which attacks tumors using the immune system, and anti-VEGF therapy, which inhibits vascular endothelial growth factor (VEGF) – a protein which, when expressed in tumors, can promote blood flow to the tumor.”

In this double-blind, global phase 3 trial, 616 patients with embolization-eligible, unresectable hepatocellular carcinoma were randomized on a 1-to-1-to-1 basis to receive durvalumab plus bevacizumab and TACE (n = 204), durvalumab plus TACE (n = 207), or TACE alone (n = 205). Patients received 1500mg of durvalumab or placebo 4 times per week, plus TACE. Following the completion of TACE, patients received 1120 mg durvalumab or placebo plus 15 mg/kg bevacizumab or placebo 3 times per week. The primary end point for this study was PFS for durvalumab plus bevacizumab and TACE vs TACE alone. Secondary end points included PFS for durvalumab plus TACE vs TACE alone, overall survival (OS), objective response rate (ORR), time to progression, and safety for durvalumab plus bevacizumab and TACE or durvalumab and TACE vs TACE.

Patients in the durvalumab, bevacizumab, and TACE arm demonstrated a significantly improved PFS vs the TACE alone arm (15.0 months vs 8.2 month; hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61 to 0.98; P = .032). There was no statistically significant difference in PFS among patients in the durvalumab plus TACE arm vs the TACE alone arm. The ORR of the durvalumab, bevacizumab, and TACE arm was 43.6%, vs 41.0% in the durvalumab plus TACE arm, and 29.6% in the TACE alone arm. The median times to progression were 22.0 months, 11. 5 months, and 10.0 months, respectively.

Of the 154 patients included in the durvalumab, bevacizumab, and TACE arm, 32.5% of patients had a maximum grade 3/4 treatment-related adverse event (15.1% of 232 in durvalumab plus TACE; 13.5% of 200 in TACE alone). There were 0 deaths due to treatment-related adverse events in the durvalumab, bevacizumab, and TACE arm, compared with 1.3% of patients in the durvalumab plus TACE arm and 2.0% in the TACE alone arm.

ASCO expert Cathy Eng, MD, stated, “These results of the EMERALD-1 trial have the potential to establish a new standard of care for the treatment of unresectable hepatocellular carcinoma, a complex disease with poor prognosis, by showing for the first time that adding an immunotherapy-based combination to TACE significantly improved progression-free survival.”

Source:

Lencioni R, Kudo M, Erinjeri J, et al. EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization. Presented at 2024 ASCO Gastrointestinal Cancer Symposium; January 18-20, 2024; San Francisco, California. Abstract LBA432

Adding Immunotherapy-Based Combination to TACE Improves Progression-Free Survival in Patients With Most Common Liver Cancer. ASCO. January 16, 2024. https://old-prod.asco.org/about-asco/press-center/news-releases/adding-immunotherapy-based-combination-tace-improves