AstraZeneca's EMERALD-1 trial is exploring the potential of immunotherapy in earlier stages of hepatocellular carcinoma (HCC). The study investigates the PD-L1 inhibitor Imfinzi (durvalumab) plus bevacizumab as an add-on therapy to transarterial chemoembolisation (TACE). The trial's initial results, presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, have sparked both excitement and questions regarding the optimal treatment approach.
The EMERALD-1 trial involved 616 patients with unresectable, loco-regional HCC, a condition characterized by a high risk of progression or recurrence within the first year of treatment. Approximately 20%-30% of the 900,000 individuals diagnosed with HCC annually are eligible for embolisation therapy. The study met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS) with the Imfinzi and bevacizumab combination compared to TACE alone.
Progression-Free Survival Improvement
The addition of Imfinzi and bevacizumab to TACE resulted in a 23% reduction in PFS. The median PFS was 15 months in the treatment group compared to 8 months with TACE alone. The time to progression (TTP) was also significantly longer in the combination arm, at 22 months versus 10 months with TACE alone. Cathy Eng, a gastrointestinal commentator at ASCO GU from Vanderbilt-Ingram Cancer Centre, noted that these results could potentially establish a new standard of care for unresectable HCC.
Questions Arise Regarding Imfinzi's Role
However, a second arm of the study, which compared Imfinzi plus TACE to TACE alone, failed to demonstrate a statistically significant improvement in PFS. This raises the possibility that the observed benefit from the triplet regimen may be primarily driven by bevacizumab, an off-patent VEGF inhibitor. Regulators may seek additional data to confirm the specific contribution of Imfinzi to the therapy's efficacy before granting approval.
Susan Galbraith, AstraZeneca’s head of oncology R&D, has previously indicated that each component of the regimen would need to demonstrate a benefit for accelerated approval based solely on PFS data. The researchers, led by Riccardo Lencioni from the Pisa University School of Medicine in Italy, are continuing to monitor patients for the secondary endpoint of overall survival (OS) and are also investigating different immune checkpoint inhibitors and embolisation-based strategies.
Future Directions and Ongoing Trials
"We are discussing [this] positive EMERALD-1 data with global regulatory authorities while awaiting the final overall survival results from the trial," commented Galbraith. AstraZeneca is also exploring other treatment options for TACE-eligible HCC patients through the EMERALD-3 study. This trial, involving 725 subjects, is evaluating Imfinzi, AstraZeneca’s CTLA4 inhibitor Imjudo (tremelimumab), Eisai’s multikinase inhibitor Lenvima (lenvatinib), and TACE. The initial data from the EMERALD-3 trial is expected next year.
