Durvalumab Treatment Regimen Reduces Risk of Disease Progression, Death in Patients With HCC

Positive results from the EMERALD-1 phase 3 trial demonstrated that compared to transarterial chemoembolization (TACE) alone, durvalumab (Imfinzi; AstraZeneca) in combination with TACE and bevacizumab (Avastin; Genentech) presented a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). These results were presented at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium in San Francisco, California.

Image credit: SciePro | stock.adobe.com

Durvalumab is a human monoclonal antibody that binds to the PD-L1 protein, blocking the interaction of PD-L1 with the PD-1 and CD80 proteins. This action counters the tumor’s immune-evading mechanism and releases the inhibition of immune responses. In combination with chemotherapy (gemcitabine plus cisplatin), durvalumab is approved for treatment in locally advanced or metastatic biliary tract cancer, and for the treatment in unresectable HCC in combination with tremelimumab (Imjudo; AstraZeneca).

Approximately 20% to 30% of patients with HCC are eligible for embolization, the standard of care for this population; however, most patients experience disease progression or recurrence within 8 months after receiving embolization. The EMERALD-1 study is a randomized, double-blind, placebo-controlled, multicenter phase 3 trial which evaluated the efficacy and safety of durvalumab plus TACE and bevacizumab in 616 patients with unresectable HCC who were eligible for embolization. The primary endpoint was PFS for the durvalumab regimen vs TACE alone, and the secondary endpoints were PFS for durvalumab plus TACE, overall survival (OS), patient-reported outcomes, and overall response rate.

“In this earlier liver cancer setting, embolization alone has been the standard of care for more than 20 years, and rates of disease progression have remained high,” said lead study investigator Bruno Sangro, MD, PhD, director of the Liver Unit and professor of medicine at Clínica Universidad de Navarra, Pamplona, in a press release.

The trial results indicated that, compared to TACE alone, treatment with durvalumab with TACE and bevacizumab reduced the risk of disease progression or death by approximately 23% (based on a hazard ratio [HR] of 0.77; 95% confidence interval [CI] 0.61-0.98; p = 0.032). In addition, the median PFS observed was 15 months in patients treated with the durvalumab regimen vs 8.2 months in those treated with TACE alone. The PFS benefit was consistent across key prespecified subgroups, and the secondary endpoint of time to progression (TTP) further supports the clinical benefit of durvalumab with TACE and bevacizumab in this patient population (durvalumab group median TTP: 22 months; TACE group median TTP: 10 months). Further, the trial will continue to further assess OS.

“Adding durvalumab and bevacizumab to TACE reduced the risk of disease progression or death by 23% for patients with liver cancer eligible for embolization, showing for the first time that combining a systemic treatment with TACE meaningfully improves this clinically relevant outcome in earlier-stage disease,” said Sangro in the press release.

In addition, the safety profile indicated that durvalumab plus TACE and bevacizumab was generally manageable and consistent with the known profiles for each treatment. The number of TACE procedures were consistent across both patient cohorts, and no new safety signals were observed. Grade 3 and 4 adverse events of any cause had occurred in approximately 45.5% of patients in the durvalumab regimen group, and 23% in the TACE group.

“With [durvalumab]-based treatment, patients with liver cancer eligible for embolization lived nearly 7 additional months before their disease progressed,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in the press release. "We are discussing these positive EMERALD-1 data with global regulatory authorities while awaiting the final [OS] results from the trial."

Reference

AstraZeneca. Imfinzi plus transarterial chemoembolisation (TACE) and bevacizumab reduced the risk of disease progression or death by 23% vs. TACE in liver cancer eligible for embolization. News release. January 19, 2024. Accessed January 24, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-with-tace-and-bevacizumab-in-patients-with-hepatocellular-carcinoma-eligible-for-embolisation.html