Clinical trialPhase 3Liver cancer

Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study

Lancet · 2025616 patients (204 durvalumab + bevacizumab, 207 durvalumab + placebo, 205 placebo)

Sangro B, Kudo M, Erinjeri JP, et al. Lancet. 2025. 405:216-232

Study type: Clinical trial
Study name: EMERALD-1
Phase: Phase 3
Design: Randomised (1:1:1), double-blind, placebo-controlled trial, 157 centres in 18 countries
Sample size: 616 patients (204 durvalumab + bevacizumab, 207 durvalumab + placebo, 205 placebo)
Source: Lancet · 2025
Trial registration: NCT03778957

In plain words

Chemoembolisation (TACE) is a treatment that delivers medicine through a catheter directly into the blood vessel feeding a liver tumour, and is used for disease confined to the liver that cannot be operated on. This study showed that adding two injected drugs (durvalumab and bevacizumab) to TACE increased the average time the disease stayed under control from about 8 months to 15 months. But it is not yet known whether this helps patients live longer. This combination is not yet an accepted standard treatment, and any decision about it should be made with the treatment team.

Key results

15.0 vs 8.2 months

Median progression-free survival: durvalumab + bevacizumab vs placebo

HR 0.77 (95% CI 0.61 to 0.98); p=0.032 (two-sided); median PFS follow-up 27.9 months

10.0 vs 8.2 months

Median progression-free survival: durvalumab + placebo vs placebo

HR 0.94 (95% CI 0.75 to 1.19); p=0.64 — not significant

44% / 41% / 30%

Objective response rate (independent review, RECIST 1.1)

Durvalumab + bevacizumab, durvalumab + placebo and placebo, respectively; full text of the paper

Not reported in this paper

Overall survival

Overall survival data will be presented in a later publication

Drugs in this study:Bevacizumab (Avastin)Durvalumab (Imfinzi)

Dose and schedule cards

TACE + durvalumab + bevacizumab (EMERALD-1; not approved)

Unresectable HCC without extrahepatic spread, amenable to TACE (1 to 4 TACE sessions within 16 weeks); Child-Pugh A to B7, ECOG 0–1On the page “Liver cancer” · Intermediate hepatocellular carcinoma: TACE plus systemic therapy (not approved)

Unresectable HCC without extrahepatic spread, amenable to TACE (1 to 4 TACE sessions within 16 weeks); Child-Pugh A to B7, ECOG 0–1

Drug	Dose	Route	Schedule
TACE period
TACE	1 to 4 sessions per institutional protocol	Intra-arterial	All sessions within 16 weeks of the first TACE
Durvalumab	1500 mg	IV	Every 4 weeks; first dose at least 7 days after the first TACE
After the last TACE
Durvalumab	1120 mg	IV	Every 3 weeks; starting at least 14 days after the last TACE
Bevacizumab	15 mg/kg	IV	Every 3 weeks, with durvalumab

Cycle length: 28 days during the TACE period; then 21 days
Duration: Until progression (mRECIST), intolerable toxicity or discontinuation criteria

Upper endoscopy within 6 months before enrollment to assess varices and bleeding risk was mandatory. Progression-free survival improved with durvalumab + bevacizumab, but durvalumab without bevacizumab gave no significant benefit; an overall survival benefit has not yet been shown, and the ESMO guideline regards it only as an option that “may be considered”.

On the page “Liver cancer” · Intermediate hepatocellular carcinoma: TACE plus systemic therapy (not approved)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1TACE + durvalumab + bevacizumab

TACE (conventional or drug-eluting beads; 1 to 4 sessions, all to be completed within 16 weeks of the first TACE with the entire tumour burden embolised; number and timing of sessions at the investigator's discretion) plus durvalumab 1500 mg IV every 4 weeks (first dose at least 7 days after the first TACE); then, from at least 14 days after the last TACE: durvalumab 1120 mg + bevacizumab 15 mg/kg IV every 3 weeks, until disease progression (clinical or radiological per mRECIST), unacceptable toxicity or withdrawal.

Dose reduction of durvalumab was not allowed; bevacizumab dose modification per the drug label or institutional practice. Upper endoscopy within 6 months before randomisation was required to assess varices and bleeding risk.

2TACE + durvalumab + placebo

The same regimen: TACE + durvalumab 1500 mg IV every 4 weeks, then durvalumab 1120 mg + bevacizumab placebo (sterile saline IV) every 3 weeks.

3TACE + placebo (control group)

TACE + durvalumab placebo (sterile saline or dextrose solution IV) every 4 weeks, then durvalumab placebo + bevacizumab placebo every 3 weeks.

Source of the regimen details: Full text of the paper (PMC12282661; Procedures section and Figure 1); abstract of the paper (Lancet 2025); ClinicalTrials.gov NCT03778957

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults aged 18 or older with HCC (confirmed by multiphase imaging or histology) not amenable to curative resection, ablation or transplantation but suitable for TACE, with a tumour burden treatable with no more than 4 TACE sessions within 16 weeks; no extrahepatic disease, Child-Pugh A to B7 liver function, ECOG 0 or 1 and at least one measurable intrahepatic lesion per mRECIST. Exclusion criteria: prior systemic therapy for HCC, prior embolisation (unless as part of curative treatment) and major portal vein thrombosis (Vp3 or Vp4). Median age 65 years; 61% Asian.

Endpoints

Primary endpoint: progression-free survival (PFS) by blinded independent central review per RECIST 1.1, for durvalumab + bevacizumab versus placebo.

Key secondary endpoints: PFS for durvalumab + placebo versus placebo, overall survival and time to deterioration of patient-reported outcomes (overall survival to be reported in a later publication).

Safety and side effects

Most common grade 3–4 adverse events: hypertension in recipients of durvalumab and bevacizumab (9 of 154; 6%), anaemia in the durvalumab + placebo group (10 of 232; 4%) and post-embolisation syndrome in the placebo group (8 of 200; 4%). Deaths from treatment-related adverse events: none with durvalumab + bevacizumab, 3 (1%) with durvalumab + placebo and 3 (2%) with placebo.

According to the full text of the paper (by treatment received): maximum grade 3 adverse events in 40% and grade 4 in 6% of recipients of durvalumab + bevacizumab, versus 27% and 1% with durvalumab + placebo and 21% and 3% with placebo; grade 3–4 bleeding in 9% of recipients of durvalumab + bevacizumab (0 and 1% in the other two groups); grade 3 proteinuria in 4%. Discontinuation because of adverse events: 28%, 13% and 8%.

Clinical significance and place in guidelines

EMERALD-1 was the first phase 3 trial to show an improvement in progression-free survival by adding immunotherapy and bevacizumab to TACE. However, overall survival is not reported in this paper, and durvalumab without bevacizumab showed no benefit. As far as we have checked, this combination is not FDA-approved for use with TACE; the AASLD 2023 guideline (published before these results) does not recommend combining systemic therapy with arterial therapies in stage B outside clinical trials. Current approval status should be checked with official sources.

Limitations

The primary endpoint was a surrogate (PFS) and overall survival data have not yet been reported; PFS in the control group (8.2 months) is shorter than in some contemporary TACE series; heterogeneity in TACE techniques between centres; most patients were Asian.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.