KEY TAKEAWAYS
- The EMERALD-1, phase 3 trial, aimed to investigate the efficacy of TACE with D and B in pts with uHCC.
- The primary endpoint was to determine PFS, and secondary endpoints included OS, ORR, TTP, and safety.
- Researchers noticed D+B+TACE as a groundbreaking achievement, demonstrating improvement in PFS over TACE in uHCC pts.
For over 20 years, transarterial chemoembolization (TACE) has been the standard of care for individuals with embolization-eligible unresectable hepatocellular carcinoma (uHCC). Despite this, a significant proportion of uHCC patients (pts) treated with TACE experience disease progression within 1 year. TACE induces a proinflammatory tumor microenvironment and heightens vascular endothelial growth factor (VEGF) signals.
Riccardo Lencioni and his team aimed to evaluate the therapeutic potential of immune checkpoint inhibitors (ICIs) (ICIs; e.g. D) and VEGF inhibitors (e.g. B) +TACE in advanced uHCC.
Researchers performed an inclusive analysis in EMERALD-1 (double-blind, global, Phase 3 study). The participant cohort consisted of individuals with embolization-eligible uHCC, characterized by Child-Pugh A to B7 liver function, Eastern Cooperative Oncology Group performance status 0–1, and the absence of extrahepatic disease.
Randomization occurred in a 1:1:1 ratio to the D+B+TACE, D+TACE, or TACE arms. The TACE procedures utilized were conventional (cTACE) or drug-eluting bead (DEB-TACE), based on investigator discretion.
Participants received durvalumab (D) at a dosage of (1500 mg) or a placebo for D on a Q4W schedule, concomitant with TACE. After the completion of the last TACE session, participants were administered D (1120 mg) or a placebo for D plus bevacizumab (B) (15 mg/kg) or a placebo for B (Q3W).
The primary endpoint of the study was the evaluation of progression-free survival (PFS) for the D+B+TACE vs TACE. Secondary endpoints encompassed PFS for the D+TACE vs TACE, overall survival (OS), objective response rate (ORR), time to progression (TTP), and the safety profile of D+B+TACE or D+TACE vs TACE. The assessment of PFS, ORR, and TTP was conducted through a blinded independent central review employing RECIST v1.1 criteria.
About 616 pts were enrolled, comprising BCLC Stage A (25.8%), Stage B (57.3%), and Stage C (16.1%) categories, with randomization into D+B+TACE (n=204), D+TACE (n=207), or TACE (n=205) arms. Demographic and baseline characteristics were generally balanced across the three arms.
The primary objective was achieved, demonstrating a significant improvement in PFS for D+B+TACE vs TACE (median [m] PFS 15.0 vs. 8.2 months [mo]; hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.98; p=0.032 [threshold 0.0434]). Consistency in results was observed across most prespecified subgroups. The secondary endpoint of PFS for D+TACE vsTACE did not reach statistical significance (mPFS 10.0 vs. 8.2 mo; HR, 0.94; 95% CI, 0.75–1.19; p=0.638).
The ORR was 43.6%, 41.0%, and 29.6%, while the mTTP was 22.0, 11.5, and 10.0 mo for D+B+TACE, D+TACE, and TACE, respectively. No new safety signals emerged, and in the safety analysis sets for D+B+TACE (n=154), D+TACE (n=232), and TACE (n=200), 32.5%, 15.1%, and 13.5% of pts experienced maximum Grade 3/4 treatment-related adverse events (TRAEs). Discontinuation due to TRAEs occurred in 8.4%, 4.3%, and 3.5% of pts, and TRAE-related deaths were reported in 0%, 1.3%, and 2.0%. Patients continue to be monitored for OS.
The study concluded that D+B+TACE represented a groundbreaking milestone as the first immune checkpoint inhibitor (ICI)-based regimen in a global Phase 3 trial, demonstrating both statistically significant and clinically meaningful improvement in PFS vs TACE alone for pts with embolization-eligible uHCC. The safety profile of D+B+TACE proved manageable and remained consistent with established safety profiles of D, B, and TACE in uHCC.
The study is sponsored by AstraZeneca
Source: https://meetings.asco.org/abstracts-presentations/229367
Clinical Trial: https://clinicaltrials.gov/study/NCT03778957
Lencioni R, Kudo M, Erinjeri J, et al. (2023).”EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization.” Presented at ASCO (Abstract LBA432).
