EMERALD-1: Durvalumab and Bevacizumab Plus TACE Improves PFS in Patients With Unresectable HCC

Adding durvalumab and bevacizumab to a well-known therapeutic procedure boosted progression-free survival (PFS) by almost 7 months for eligible patients with unresectable hepatocellular carcinoma (uHCC), according to results being presented today.

Results from EMERALD-1, the trial evaluating use of the new treatment combination, are being presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI), which is being held through tomorrow in San Francisco, California.

Transcatheter arterial chemoembolization (TACE), has been the current standard of care for 20 years for patients with uHCC who can receive embolization. The process involves targeting tumors by cutting off their blood supply while aiming chemotherapy directly at the tumor. About 20% to 30% of patients with uHCC, the most common liver cancer worldwide, can receive the treatment, according to ASCO.

Despite improvements in TACE over the years, recurrence is common, and experts including the lead author of EMERALD-1 have examined whether TACE itself “may create conditions that permit or even courage angiogenesis,” according to a review published in 2013. In particular, authors of EMERALD-1 write, “Embolization creates a proinflammatory tumor microenvironment and increases VEGF signals.”

Riccardo Lencioni, MD | Image: Pisa University

Thus, investigators led by Riccardo Lencioni, MD, from the Pisa University School of Medicine in Pisa, Italy, evaluated using TACE in combination with other therapies that could reduce these effects.

“Research in other studies suggested that TACE would work well with 2 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,” Lencioni said in a statement.

EMERALD-1 is a double-blind phase 3 study that enrolled 616 patients eligible for embolization to treat unresectable HCC. Patients were randomized in 3 groups: the first received the immune checkpoint inhibitor durvalumab (Imfinzi, AstraZeneca) plus the anti-VEGF bevacizumab and TACE (204 patients), the second received durvalumab plus TACE (207 patients), and third received TACE alone (205 patients). More than half the patients in the study (57.3%) had cancers in the intermediate stage, based on the Barcelona Clinic Liver Cancer (BCLC) staging system, which meant the liver had mild to moderate damage. Another 25.8% still had liver function, per BCLC, while 16.1% had severe liver damage.

The primary end point was PFS for the first group. Secondary end points included PFS for the other 2 groups, as well as overall survival (OS), objective response rate (ORR), time to progression (TTP), and safety for all 3 arms. End points besides safety were evaluated by blinded independent central review.

Key results were as follows:

• Patients treated with durvalumab, bevacizumab, and TACE saw a median PFS of 15.0 months, compared with 8.2 months for those treated only with TACE, for a hazard ratio (HR) of 0.77 (95% CI, 0.61–0.98; P = .032. Results were consistent across most prespecified subgroups, the study authors reported.
• PFS favored durvalumab and TACE over TACE alone, but the difference did not reach statistical significance (10.0 months vs 8.2 months, for HR 0.94; 95% CI, 0.75–1.19; P = .638).
• ORR was also superior in the group receiving durvalumab, bevacizumab, and TACE; results were 43.6%, compared with 41.0% for the durvalumab and TACE group and 29.6% for the TACE group.
• Median TTP was 22.0 months, 11.5 months, and 10.0 months, respectively.
• Treatment-related adverse events (TRAEs) of grade 3/4 were seen in 32.5% of the durvalumab, bevacizumab, and TACE group, compared with 15.1% in the durvalumab/TACE group and 13.5% in the TACE group. Discontinuation of treatment occurred in 8.4%, 4.3%, and 3.5% of patients in each group, respectively.
• 2.0% of patients died due to TRAEs.
• Patients are still being followed for OS.

Cathy Eng, MD | Image: Vanderbilt University

Cathy Eng, MD, FACP, FASCO, who is professor of medicine, Division of Hematology and Oncology, Department of Medicine and is the co-director of GI Oncology and co-leader of the Gastrointestinal Cancer Research Program at Vanderbilt University Medical Center, said the results were encouraging.

“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,” Eng said in a statement.

Reference

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: American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January 18-20, 2024, San Francisco, CA. Abstract LBA432.