EMERALD-1: Durvalumab Plus Bevacizumab With TACE Versus TACE Monotherapy

Transarterial chemoembolization (TACE) has been the standard of care for unresectable hepatocellular carcinoma (uHCC) for more than 20 years, but many patients who receive this treatment often experience disease progression within 1 year.

At the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Dr. Riccardo Lencioni presented new data from EMERALD-1. The study analyzed TACE plus durvalumab with and without bevacizumab to determine if the combination benefits patients with uHCC who are eligible for embolization to reduce the risk of progression.

Patients with uHCC and Child-Pugh A-B7 liver function, an Eastern Cooperative Oncology Group performance status of 0-1, and no evidence of extrahepatic disease were eligible for the study. Patients were randomized 1:1:1 to 3 treatment arms: durvalumab plus bevacizumab with TACE (n=204), durvalumab plus TACE (n=207), or TACE monotherapy (n=205).

The primary end point was progression-free survival (PFS) for the durvalumab plus bevacizumab with TACE treatment arm versus TACE monotherapy. Secondary end points included PFS for the durvalumab plus TACE versus TACE monotherapy arm, overall survival (OS), objective response rate (ORR), time to progression (TTP), and safety.

The primary objective was met at final PFS analysis. Durvalumab plus bevacizumab with TACE demonstrated significantly improved PFS over TACE monotherapy, with a median PFS rate of 15.0 versus 8.2 months. The secondary end point results were not statistically significant, with ORR rates of 43.6%, 41.0%, and 29.6%, respectively, for the durvalumab plus bevacizumab with TACE, durvalumab plus TACE, and TACE monotherapy arms. The TTP rate was 22.0 months for the durvalumab plus bevacizumab with TACE arm, 11.5 months for the durvalumab plus TACE arm, and 10.0 months for the TACE monotherapy arm. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 32.5%, 15.1%, and 13.5% of patients, respectively, in the durvalumab plus bevacizumab with TACE, durvalumab plus TACE, and TACE monotherapy arms. Discontinuations due to TRAEs occurred in 8.4%, 4.3%, and 3.5% of patients, and deaths due to TRAEs occurred in 0.0%, 1.3%, and 2.0%, respectively.

Durvalumab plus bevacizumab with TACE has shown statistically significant improvement in PFS versus TACE alone, with a manageable safety profile. Patients continue to be followed for OS results.