AstraZeneca’s combination immunotherapy strategy has delivered a major clinical milestone in advanced liver cancer.
The pharma giant's EMERALD-3 Phase III trial showed a statistically significant improvement in progression-free survival (PFS) and an encouraging overall survival (OS) trend in patients with unresectable hepatocellular carcinoma (HCC) eligible for embolisation.
The study evaluated Imfinzi (durvalumab) plus Imjudo (tremelimumab) — the STRIDE regimen — alongside the targeted therapy lenvatinib and transarterial chemoembolisation (TACE), compared with TACE alone.
The most intensive treatment arm — STRIDE plus lenvatinib and TACE — reduced the risk of disease progression or death by 30%, meeting the primary endpoint for PFS with a hazard ratio of 0.70. Median PFS improved to 13.0 months versus 9.8 months with TACE alone, with consistent benefit across patient subgroups.
While overall survival data remain immature, the results pointed to a favourable trend. In this arm, OS showed a hazard ratio of 0.84, indicating a directional improvement but not statistical significance at this interim stage.
A second investigational arm — STRIDE plus TACE without lenvatinib — also demonstrated benefit versus TACE alone, with a 29% reduction in risk of progression or death. Median PFS reached 12.9 months compared with 8.1 months for TACE alone. This arm also showed an early survival advantage, with OS improving.
Across both regimens, Kaplan-Meier curves showed durable benefit extending beyond one year, with 24-month PFS rates reaching up to 30.4% in the lenvatinib-containing arm versus 19.3% for TACE alone.
A planned exploratory comparison between the two investigational strategies suggested a possible advantage for the lenvatinib-containing regimen in patients with non-viral disease though further follow-up is ongoing.
Ghassan Abou-Alfa, Attending Physician, Professor of Medicine at Memorial Sloan Kettering Cancer Center and principal investigator in the trial, said: “Patients with embolisation-eligible liver cancer face the burden of repeated localised therapy and are in urgent need of new systemic treatment options to delay disease progression and recurrence.
"The EMERALD-3 trial represents a meaningful advance for patients, with nearly one in three alive and progression-free at two years when treated with this dual immunotherapy regimen with or without lenvatinib, with a trend toward improved survival.”
Susan Galbraith, Executive Vice President, Oncology Haematology R&D at AstraZeneca, said: “Building on practice-changing results from the HIMALAYA Phase III trial, these progression-free survival results and the early overall survival trend in the EMERALD-3 trial highlight the meaningful impact of bringing the STRIDE regimen into an earlier setting.
"These results advance our strategy to move novel immunotherapy regimens into earlier stages of cancer and underscore the opportunity to bring new treatment options for patients into this challenging liver cancer setting.”
