AstraZeneca's ambitious attempt to expand immunotherapy into earlier stages of liver cancer has yielded mixed results in a pivotal clinical trial. The EMERALD-1 study, presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, evaluated the addition of Imfinzi (durvalumab) and bevacizumab to transarterial chemoembolisation (TACE) in patients with unresectable, loco-regional hepatocellular carcinoma (HCC).
The triple combination therapy demonstrated a significant improvement in progression-free survival (PFS), achieving a median of 15 months compared to 8 months with TACE alone – representing a 23% reduction in progression risk. The time to progression was notably extended to 22 months, more than double the 10 months observed with standard TACE therapy.
Complex Efficacy Picture Emerges
A crucial finding from the study has raised important questions about the therapeutic contribution of individual components. While the triple combination showed clear benefits, a separate arm testing Imfinzi plus TACE failed to demonstrate statistically significant PFS improvement compared to TACE alone. This outcome suggests that bevacizumab might be the key driver of the observed benefits in the triple combination.
Trial Design and Patient Population
The EMERALD-1 trial enrolled 616 patients with unresectable, loco-regional HCC, a condition that typically carries a high risk of disease progression or recurrence within the first year of treatment. This patient population represents a significant subset of the approximately 900,000 annual HCC diagnoses worldwide, with 20-30% of patients typically eligible for embolisation therapy.
Expert Perspectives and Future Directions
Dr. Cathy Eng from Vanderbilt-Ingram Cancer Centre provided an optimistic assessment, stating that the results "have the potential to establish a new standard of care for the treatment of unresectable hepatocellular carcinoma."
However, the mixed results may complicate the regulatory pathway. Dr. Susan Galbraith, AstraZeneca's head of oncology R&D, acknowledged that demonstrating individual component benefits would likely be necessary for accelerated approval based on PFS data alone. The company is currently in discussions with global regulatory authorities while awaiting final overall survival results.
Additional Research Underway
AstraZeneca is not putting all its eggs in one basket. The company is simultaneously conducting the EMERALD-3 study, a 725-patient trial investigating a different combination approach. This study evaluates Imfinzi alongside AstraZeneca's CTLA4 inhibitor Imjudo (tremelimumab), Eisai's multikinase inhibitor Lenvima (lenvatinib), and TACE in similar patient populations. Initial results from this trial are expected next year.
The research team, led by Dr. Riccardo Lencioni from Pisa University School of Medicine, continues to explore various immune checkpoint inhibitors and embolisation-based approaches while monitoring ongoing survival data from EMERALD-1.
