The safety profile of durvalumab plus TACE and bevacizumab in patients with hepatocellular carcinoma in the phase 3 EMERALD-1 study appears to consistent with previous findings.
Patients with hepatocellular carcinoma (HCC) who were eligible for embolization and received treatment with durvalumab (Imfinzi) plus transarterial chemoembolization (TACE) and bevacizumab (Avastin) experienced a statistically significant and clinically meaningful progression-free survival (PFS) benefit over TACE by itself, according to a press release on data from the phase 3 EMERALD-1 study (NCT03778957) from developer AstraZeneca.1
This improvement in PFS met the trial’s primary end point. The safety profile of each individual component of the regimen was consistent with previous reports. Findings from the trial are set to be presented at an upcoming medical meeting and will be submitted to regulatory authorities.
Moreover, the developer intends to assess durvalumab in several other gastrointestinal malignancies, including combining the agent with bevacizumab in the adjuvant setting for those with HCC at a high risk of recurrence as part of the phase 3 EMERALD-2 study (NCT03847428). Additionally, the agent will be evaluated in combination with tremelimumab-actl (Imjudo), lenvatinib (Lenvima), and TACE for locoregional HCC eligible for embolization in the phase 3 EMERALD-3 study (NCT05301842).
“Patients with liver cancer eligible for embolization experience high rates of progression or recurrence and do not have the opportunity for early intervention with effective systemic therapy,” principal investigator Riccardo Lencioni, MD, FSIR, EBIR, professor and director of the Cancer Imaging Program in the Department of Diagnostic and Interventional Radiology at Pisa University Hospital in Pisa, Italy, said in the 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 randomized, double-blind, placebo controlled, multicenter study includes 600 patients who were randomly assigned 1:1:1 to receive either drug-eluting bead (DEB)–TACE or conventional TACE (cTACE) plus durvalumab and durvalumab/placebo after last TACE procedure; DEB-TACE or cTACE plus durvalumab followed by durvalumab/bevacizumab; or DEB-TACE or cTACE alone.2
To be included, patients needed to have confirmed disease that was not amenable to curative intent treatment, a Child-Pugh score ranging from A to B7, and an ECOG performance status of 0 to 1. Those with a history of nephrotic or nephritic syndrome, clinically significant cardiovascular disease, extrahepatic disease, or main portal vein thrombosis were not able to enroll on the study. Those with active or previous hepatitis B or C infection are eligible to enroll on the study.
The study’s primary end point was PFS in arm A compared with arm C, with key secondary end points including PFS in arms B and C, overall survival, health-related quality of life, and safety.
“These positive results for [durvalumab]-based treatment in EMERALD-1 may bring the potential of immunotherapy to patients with earlier stages of liver cancer. 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,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, concluded.1