Results from two Phase III trials presented at the 2026 ESMO Gastrointestinal Cancers Congress have highlighted both the promise and the remaining uncertainty surrounding the use of immunotherapy-based combinations with transarterial chemoembolisation (TACE) for patients with embolisation-eligible hepatocellular carcinoma (HCC).
While the EMERALD-1 trial found that an earlier progression-free survival (PFS) benefit did not translate into improved overall survival (OS), the EMERALD-3 study reported encouraging improvements in PFS and tumour response with a STRIDE-based regimen. However, mature OS data from EMERALD-3 are still awaited.
Together, the findings suggest that although TACE-immunotherapy combinations continue to show clinical promise, their impact on long-term survival remains to be established.
EMERALD-1: PFS benefit not reflected in overall survival
The double-blind, placebo-controlled Phase III EMERALD-1 trial enrolled 616 patients with unresectable, embolisation-eligible HCC who were randomised to receive durvalumab plus bevacizumab with TACE, durvalumab with TACE, or TACE alone.
The study previously met its primary endpoint, demonstrating a significant improvement in PFS with durvalumab plus bevacizumab plus TACE compared with TACE alone. Published in 2025, the earlier analysis reported a median PFS of 15.0 months versus 8.2 months (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.61–0.98; p=0.032). 
However, the final OS analysis presented at this year’s congress showed no statistically significant survival advantage for either immunotherapy-containing regimen.
After a median follow-up of 56.3 months in the durvalumab plus bevacizumab arm, 57.8 months in the durvalumab arm and 53.0 months in the TACE-alone arm, median OS was 29.9 months, 33.6 months and 33.3 months, respectively. Compared with TACE alone, the hazard ratio for OS was 1.10 (95% CI 0.87–1.39; p=0.470) for durvalumab plus bevacizumab and 0.93 (95% CI 0.74–1.19; p=0.666) for durvalumab alone.
The addition of systemic therapy was also associated with increased toxicity. Grade 3/4 adverse events occurred in 47.4% of patients receiving durvalumab plus bevacizumab plus TACE, compared with 30.6% in the durvalumab plus TACE group and 25.0% in the TACE-alone group. Treatment discontinuation due to adverse events occurred in 29.2%, 12.9% and 8.5% of patients, respectively.
The investigators concluded that, despite the previously reported improvement in PFS, durvalumab with or without bevacizumab did not improve overall survival compared with TACE alone.
EMERALD-3: Encouraging efficacy signals, but survival data pending
The Phase III EMERALD-3 study evaluated a STRIDE (Single Tremelimumab Regular Interval Durvalumab)-based approach with TACE, with or without lenvatinib, in 760 patients with embolisation-eligible HCC.
The primary endpoint was PFS assessed by blinded independent central review.
STRIDE plus lenvatinib plus TACE met the primary endpoint, significantly improving PFS compared with TACE alone (HR 0.70; 95% CI 0.57–0.86; p=0.0007). The STRIDE plus TACE arm also demonstrated a clinically meaningful improvement in PFS (HR 0.71; 95% CI 0.56–0.91). Both experimental regimens also achieved higher tumour response rates than TACE alone.
Using RECIST v1.1 criteria, objective response rates were 38.9% with STRIDE plus lenvatinib plus TACE and 40.8% with STRIDE plus TACE, compared with 27.0% for TACE alone. When assessed using mRECIST, objective response rates increased to 65.7%, 55.4% and 41.7%, respectively.
Median duration of response was also numerically longer with the STRIDE-based regimens than with TACE alone. Overall survival data from EMERALD-3 were not mature at the time of this analysis.
The investigators concluded that the findings further support a STRIDE-based regimen with TACE as a potential new treatment for patients with embolisation-eligible HCC.
Long-term benefit remains the key question
Taken together, the EMERALD programme reflects the rapid evolution of systemic therapy in intermediate-stage HCC, while also highlighting the importance of mature survival data when evaluating new treatment strategies.
EMERALD-1 demonstrated that an improvement in progression-free survival did not ultimately translate into longer overall survival, despite positive findings in the primary analysis. By contrast, EMERALD-3 has demonstrated encouraging improvements in disease control and tumour response, but whether these benefits will result in a meaningful survival advantage remains unknown until final OS results become available.
As immunotherapy continues to move into earlier stages of HCC management, the mature outcomes from EMERALD-3 are expected to help define the future role of STRIDE-based TACE combinations in clinical practice.
References:
Overall survival in EMERALD-1: A Phase III study of durvalumab ± bevacizumab and transarterial chemoembolisation in participants with unresectable embolisation-eligible hepatocellular carcinoma. Presented at the ESMO Gastrointestinal Cancers Congress 2026. Abstract 183O.
Tumour response analyses by RECIST v1.1 and mRECIST in the Phase III EMERALD-3 study of STRIDE with or without lenvatinib plus transarterial chemoembolisation in embolisation-eligible hepatocellular carcinoma. Presented at the ESMO Gastrointestinal Cancers Congress 2026. Late-breaking Abstract LBA2.
