Durvalumab plus concurrent transarterial chemoembolization followed by durvalumab with bevacizumab resulted in a significant improvement in PFS over TACE alone in patients with hepatocellular carcinoma who are eligible for embolization, meeting the primary end point of the phase 3 EMERALD-1 trial.
Durvalumab (Imfinzi) plus concurrent transarterial chemoembolization (TACE) followed by durvalumab with bevacizumab (Avastin) resulted in a significant improvement in progression-free survival (PFS) over TACE alone in patients with hepatocellular carcinoma (HCC) who are eligible for embolization, meeting the primary end point of the phase 3 EMERALD-1 trial (NCT03778957).1
The toxicity profile for the regimen was in line with what has previously been reported with each agent. No new safety signals were observed.
Findings will be shared at a future medical meeting and discussed with regulatory authorities. Moreover, the trial will continue to follow the secondary end point of overall survival (OS).
“Patients with liver cancer [who are] eligible for embolization experience high rates of progression or recurrence and do not have the opportunity for early intervention with effective systemic therapy,” Riccardo Lencioni, MD, FSIR, EBIR, professor and director of the Cancer Imaging Program in the Department of Diagnostic and Interventional Radiology of Pisa University Hospital in Pisa, Italy, stated in a press release. “These results for durvalumab plus bevacizumab have the potential to reshape the treatment of this complex disease with a poor prognosis by showing for the first time that adding an immunotherapy combination to TACE significantly improves PFS.”
The double-blind, placebo-controlled, multicenter, global trial enrolled patients with histologically or radiologically confirmed HCC that was not amenable to curative treatment.2,3 They needed to be at least 18 years of age, have a Child-Pugh score of A to B7, an ECOG performance status of 0 or 1, measurable disease by RECIST criteria, and acceptable organ and bone marrow function. They could not have evidence of extrahepatic disease.
If they had a history of nephrotic or nephritic syndrome, clinically significant cardiovascular disease, a history of arterioembolic events, or evidence of main portal vein thrombosis, they were excluded. They also could not have prior or current evidence of coagulopathy or bleeding diathesis within 28 days after surgery, or gastrointestinal (GI) perforation or active GI bleeding within 6 months of trial enrollment.
Study participants (n = 616) were randomly assigned 1:1:1 to receive durvalumab plus TACE (arm A), durvalumab plus TACE and bevacizumab (arm B), or placebo plus TACE (arm C).3 Durvalumab or the matched placebo was given at least 7 days after the initial TACE procedure. Bevacizumab or the matched placebo was combined with durvalumab or the matched placebo at least 2 weeks after the last TACE procedure.
In addition to PFS by blinded independent central review assessment for arm B vs arm C serving as the trial’s primary end point, secondary end points included PFS for arm A vs arm C; OS; objective response rate; and patient-reported outcomes with regard to deterioration in global health status or quality of life, functioning, and symptoms as well as deterioration in symptoms.1,2
Other end points of interest include safety, immunogenicity, and pharmacokinetic assessments.
“These positive results for [durvalumab]-based treatment in EMERALD-1 may bring the potential of immunotherapy to patients with earlier stages of liver cancer,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, stated in a press release.1 “We look forward to discussing these data with regulatory authorities and seeing the survival data mature over time, which will be important as we aim to bring this novel treatment option to patients.”