In the phase III EMERALD-1 trial reported in The Lancet, Sangro et al found that transarterial chemoembolization (TACE) with durvalumab/bevacizumab improved progression-free survival vs placebo in patients with unresectable hepatocellular carcinoma (HCC) amenable to embolization.
Study Details
In the double-blind study, 616 patients from sites in 19 countries were randomly assigned between November 2018 and July 2021 to TACE plus durvalumab/bevacizumab (n = 204), durvalumab plus placebo (n = 207), or placebo alone (n =205). Durvalumab was given at 1,500 mg every 4 weeks and then at 1,120 mg; bevacizumab was given at 15 mg/kg every 3 weeks. Overall, 61% of enrolled patients were Asian and 29% were White. The primary endpoint of the trial was progression-free survival on blinded independent central review.
Key Points
At data cutoff in September 2023, median follow-up for progression-free survival was 27.9 months (95% confidence interval [CI] = 27.4–30.4 months). Median progression-free survival was 15.0 months (95% CI = 11.1–18.9 months) with durvalumab/bevacizumab vs 8.2 months (95% CI = 6.9–11.1 months) with placebo (hazard ratio [HR] = 0.77, 95% CI = 0.61–0.98, P = .032), and 10.0 months (95% CI = 9.0–12.7 months) with durvalumab and placebo (HR vs placebo = 0.94, 95% CI = 0.75–1.19, P = .64).
Grade 3 or 4 adverse events occurred in 45% of the patients in the durvalumab/bevacizumab group (most commonly hypertension [6%] and anemia [5%]), 28% of those in the durvalumab/placebo group (most commonly anemia [4%]) and 23% of those in the chemotherapy group (most commonly postembolization syndrome [4%]). Treatment-related death occurred in no patients in the durvalumab/bevacizumab group, three patients in the durvalumab/placebo group (due to arterial hemorrhage, liver injury, and multiple organ dysfunction syndrome in one each), and three patients in the chemotherapy group (due to esophageal varices hemorrhage, upper gastrointestinal hemorrhage, and dermatomyositis in one each).
The investigators concluded, “Durvalumab plus bevacizumab plus TACE has the potential to set a new standard of care. With additional follow-up of the EMERALD-1 study, future analyses, including the final overall survival data and patient-reported outcomes, will help to further characterize the potential clinical benefits of durvalumab plus bevacizumab plus TACE in hepatocellular carcinoma amenable to embolization.”
Bruno Sangro, PhD, of the Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra, Pamplona, Spain, is the corresponding author for The Lancet article.
Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit thelancet.com.
