TACE Plus Durvalumab and Bevacizumab Could Alter SOC in Embolization-Eligible, Unresectable HCC

Treatment with the combination of transarterial chemoembolization (TACE), durvalumab (Imfinzi), and bevacizumab (Avastin) could represent a new standard of care for patients with unresectable hepatocellular carcinoma (HCC) who are eligible for embolization, according to Riccardo Lencioni, MD.

Findings from the final progression-free survival (PFS) analysis of the phase 3 EMERALD-1 trial (NCT03778957) presented at the 2024 Gastrointestinal Cancers Symposium showed TACE plus durvalumab and bevacizumab (n = 204) elicited a median PFS of 15.0 months (95% CI, 11.1-18.9) vs 8.2 months (95% CI, 6.9-11.1) with TACE plus placebos (n = 205), translating to a 23% reduction in the risk of progression or death (HR, 0.77; 95% CI, 0.61-0.98; stratified log-rank P = .032).

“The [PFS] data are very compelling,” Lencioni, the lead study author, said in an interview with OncLive®. “The study is still ongoing for the secondary end point of overall survival [OS], which was immature at the interim [OS] analysis and did not reach statistical significance.”

In the interview, Lencioni discussed the design of EMERALD-1, expanded on the study’s key findings, and emphasized the need to a multidisciplinary approach for treating patients with HCC. Lencioni is a professor in the Department of Surgery, Medical, Molecular, and Critical Area Pathology at Università di Pisa in Italy.

OncLive: What was the rationale for investigating the addition of durvalumab and bevacizumab to TACE in the EMERALD-1 study?

Lencioni: [The study had] a patient population that included [those] who were ineligible for radical therapies, including surgery or ablation, but had disease that was still confined to the liver. These patients account for [approximately] 20% to 30% of patients diagnosed with HCC each year worldwide.

For these patients, [in the past] 20 years, the standard of care has been TACE. There is a strong rationale from experimental studies that support the potential synergistic effect of TACE with drugs that inhibit VEGF, as well as with checkpoint inhibitors. The EMERALD-1 study investigated the combination of TACE with durvalumab plus or minus bevacizumab in patients eligible for TACE.

Could you expand on the design of the study?

The study design included 3 treatment arms. Arm A was TACE plus durvalumab, followed by durvalumab plus a placebo [for bevacizumab]. In arm B, patients received TACE plus durvalumab, followed by durvalumab plus bevacizumab. In arm C, the control arm, TACE [was added to] placebo, followed by placebos [for durvalumab and bevacizumab].

What key findings were derived from this study and presented at the 2024 symposium?

The study met its primary end point. The combination of durvalumab and bevacizumab with TACE resulted in a statistically significant and clinically meaningful improvement in PFS with respect to TACE plus placebo.

The median [PFS] was improved by 6.8 months from 8.2 months in the control arm—which is one of the best reported results for TACE [alone] in the setting of a global trial—up to 15.0 months with the combination of durvalumab, bevacizumab, and TACE. [The PFS] benefit appears to be consistent across different subgroups. Particularly, we observed a benefit both in patients with limited tumor burden within the up-to-7 criteria and those with more extensive dissemination beyond the up-to-7 criteria.

Were there any notable safety findings seen in the investigation?

The safety appears to be manageable; adverse effects were in line with the known safety profiles of durvalumab, bevacizumab, and TACE, [and] no new or unexpected safety signals [were observed].

What next steps do you hope to see taken with this research?

This trial has opened a new horizon, showing for the first time that the combination of a locoregional, liver-directed therapy with a systemically active drug can provide a statistically significant and clinically meaningful benefit for our patients.

What unmet needs remain for patients with unresectable HCC?

HCC remains a very complex disease with a poor prognosis. However, the [treatment] armamentarium for patients with this disease has substantially increased over the past few years.

What is truly important is a multidisciplinary approach to the disease [with] an assessment that includes the entire spectrum of therapies that are currently available, [including] surgery, transplantation, ablation, embolization therapies, and this new and growing chapter of immunotherapy-based systemic therapies.

We need to be reminded that patients with HCC typically have 2 diseases: the tumor and the underlying chronic liver disease. Therefore, patient selection is extremely important, particularly regarding liver function and the risk of bleeding. An individual assessment of the individual characteristics of the patient is of utmost importance for any treatment choice in the setting of HCC.

Reference

Lencioni R, Kudo M, Erinjeri J, et al. EMERALD-1: a phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization. J Clin Oncol. 2024;42(suppl 3):LBA432. doi:10.1200/JCO.2024.42.3_suppl.LBA432