- Design
- Global, randomised, open-label, sponsor-blinded phase 3 trial
- Population
- 760 adults with embolisation-eligible HCC, Child-Pugh A
- Primary outcome
- Progression-free survival, STRIDE + lenvatinib + TACE vs TACE
- Effect
- 13.0 vs 9.8 months; HR 0.70 (0.57 to 0.86); OS HR 0.84 (0.65 to 1.09)
EMERALD-3, a global open-label phase 3 trial in The Lancet Oncology (September 2026), randomised 760 people with embolisation-eligible hepatocellular carcinoma and Child-Pugh A liver function (72% Asian) to TACE alone, TACE with STRIDE (single-dose tremelimumab plus durvalumab), or TACE with STRIDE and lenvatinib.
Median progression-free survival was 13.0 months with STRIDE-lenvatinib-TACE against 9.8 months with TACE (HR 0.70, 95% CI 0.57 to 0.86). STRIDE-TACE also improved it against the first 175 TACE patients (12.9 vs 8.1 months; HR 0.71). Overall survival at a median 24.6 months was 39.5 against 34.7 months (HR 0.84, 0.65 to 1.09), not significant. Serious adverse events occurred in 64% with the triplet, 51% with STRIDE-TACE and 23% with TACE; seven treatment-related deaths occurred with the triplet, including two from myocarditis.
Progression-free survival is a surrogate in a disease where survival after TACE is already long, and the overall survival data are immature. The triplet's toxicity is substantial; STRIDE-TACE without lenvatinib gave a similar progression-free gain with fewer serious adverse events and no treatment-related deaths.
For now this is a new option to discuss, not yet a new standard, pending overall survival.
- Discuss STRIDE-based combinations with TACE for embolisation-eligible HCC with Child-Pugh A function, once available
- Weigh the triplet's toxicity: serious adverse events in 64% and seven treatment-related deaths
- Consider that STRIDE-TACE without lenvatinib gave a similar progression-free gain with fewer harms
- Monitor for immune myocarditis and hepatic decompensation on combination therapy
- Await overall survival before treating this as the new standard
Why it matters
It is the first phase 3 evidence that immunotherapy can extend disease control when combined with TACE for intermediate-stage liver cancer.
Don't overread it
Progression-free survival improved; overall survival did not differ significantly at this analysis.
The statistics, in plain English
A hazard ratio of 0.70 for progression-free survival means a 30% lower rate of progression or death at any time. The overall survival HR of 0.84 has an interval from 0.65 to 1.09, which includes no effect.
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