In the treatment of patients with unresectable embolization-eligible hepatocellular carcinoma (eeHCC), combining transarterial chemoembolization (TACE) with the immunotherapy-based STRIDE (single tremelimumab regular interval durvalumab) regimen with or without lenvatinib substantially increases progression-free survival (PFS), as shown in the global phase 3 EMERALD-3 study.
Median PFS was 13 months with STRIDE plus lenvatinib plus TACE (STRIDE+L+TACE) vs 9.8 months with TACE alone, translating to a 30-percent reduction in the risk of progression or death (hazard ratio [HR], 0.70, 95 percent confidence interval [CI], 0.57–0.86; p=0.0007), reported lead investigator Dr Ghassan Abou-Alfa from Memorial Sloan Kettering Cancer Center in New York, New York, US. [ASCO 2026, abstract LBA4000]
STRIDE+L+TACE also showed a favourable overall survival (OS) trend compared with TACE alone at interim analysis, with a median OS of 39.5 vs 34.7 months, respectively, Abou-Alfa said. “OS maturity was at 40.3 percent.”
The 2-year PFS rates were 30.4 percent with STRIDE+L+TACE and 19.3 percent with TACE alone, and the 2-year OS rates were 66.9 percent and 61.5 percent, respectively.
“TACE has been a global standard of care for unresectable eeHCC for over 20 years, while STRIDE is a frontline standard of care in advanced HCC,” noted Abou-Alfa. “EMERALD-3 is the first phase 3 study to demonstrate that a STRIDE-based regimen improves clinical outcomes when combined with TACE, supporting its role as a potential new treatment option in unresectable eeHCC.”
EMERALD-3 design
EMERALD-3 enrolled patients with HCC not amenable to curative treatment but eligible for embolization. Patients were required to have Child-Pugh class A liver function, ECOG performance status of 0 or 1, no extrahepatic disease, no portal vein thrombosis (Vp3 or Vp4), and received no prior systemic therapy.
A total of 760 patients (83.2 percent male, 72.1 percent Asian) were randomly assigned to receive STRIDE+L+TACE (n=293, median age 67 years), STRIDE plus TACE (STRIDE+TACE; n=175, median age 65 years), or TACE alone (n=292, median age 65 years).
The primary endpoint was PFS, assessed by blinded independent central review (BICR) for STRIDE+L+TACE vs TACE alone. Key secondary endpoints included OS for STRIDE+L+TACE vs TACE alone, and PFS and OS for STRIDE+TACE vs TACE alone.
Abou-Alfa pointed out that a hierarchical multiple-testing procedure was implemented, wherein PFS for STRIDE+L+TACE vs TACE was assessed at first data cutoff and OS for STRIDE+L+TACE vs TACE would be assessed at second data cutoff provided that the PFS endpoint was met. PFS and OS for STRIDE+TACE vs TACE would then be assessed only upon meeting the preceding endpoints.
STRIDE+TACE vs TACE
Median PFS was 12.9 months with STRIDE+TACE vs 8.1 months with TACE alone, corresponding to a 29-percent reduction in the risk of progression or death (HR, 0.71, 95 percent CI, 0.56–0.91; p=0.0062). Median OS was not calculable for STRIDE+TACE vs 32.9 months for TACE (HR, 0.70, 95 percent CI, 0.51–0.95; p=0.0233). OS maturity was at 45.4 percent.
The 2-year PFS rates were 30 percent in the STRIDE+TACE arm and 20.3 percent in the TACE arm, and the 2-year OS rates were 68 percent and 57.8 percent, respectively.
Subgroup analyses
The PFS benefit with the combination strategies vs TACE alone was observed across subgroups defined by geographic region, baseline tumour burden, virology status, viral aetiology, and ALBI grade.
Abou-Alfa noted that patients in Japan had a more favourable PFS with STRIDE+L+TACE than with STRIDE+TACE relative to TACE alone.
In a preplanned analysis comparing STRIDE+L+TACE with STRIDE+TACE, there was no significant difference in PFS seen across subgroups, he added. “For the viral aetiology, there was a tad of improvement with STRIDE+L+TACE.”
Response and safety
Objective response rates were 38.9 percent with STRIDE+L+TACE and 40.8 percent with STRIDE+TACE vs 27 percent with TACE alone (odds ratios, 0.92 and 1.81, respectively). Responses, according to Abou-Alfa, were driven by partial response and stable disease.
Median duration of response was 15.7, 18.4, and 16.6 months in the STRIDE+L+TACE, STRIDE+TACE, and TACE arms, respectively.
“The safety profile was acceptable and consistent with the known safety profile of STRIDE, lenvatinib, and TACE,” said Abou-Alfa.
Grade 3 or 4 adverse events (AEs) occurred in 71.4 percent of patients in the STRIDE+L+TACE arm, 64 percent in the STRIDE+TACE arm, and 28.6 percent in the TACE arm. The most common grade 3 or 4 AEs were hypertension, postembolization syndrome, AST or lipase elevation, hypokalemia, and anaemia. Serious AEs were documented in 64.1 percent, 50.9 percent, and 23.4 percent of patients in the respective arms.
AEs led to interruption or discontinuation of any of the study drugs for 84 percent and 35.5 percent of patients in the STRIDE+L+TACE arm and 44 percent and 20.6 percent of those in the STRIDE+TACE arm, respectively.