(28) Updates and Future Directions on Combination Transarterial Chemoembolization and Immunotherapies for HCC

Marshal King, DO – Interventional Radiology Resident, The Ohio State University Wexner Medical Center; Mina Makary, MD – Interventional Radiology Attending, The Ohio State University Wexner Medical Center

Purpose: Hepatocellular carcinoma (HCC) remains the third leading cause of cancer related mortality with limited efficacy of available treatments for those presenting in later stages. Transarterial chemoembolization (TACE), a first line locoregional therapy for intermediate stage disease, allows for the simultaneous embolization of a tumors arterial supply and direct delivery of chemotherapy. The combination of TACE with immunotherapy aims to take advantage of the proposed increased tumor-associated antigens exposed during TACE. This report will provide an update on TACE combined with immunotherapy by focusing on recent data from the EMERALD-1 and LEAP-012 clinical trials and discuss future directions with the ongoing EMERALD-3 clinical trial.

Material and Methods: ClinicalTrials.gov and the PubMed Database were reviewed for recent combination TACE and immunotherapy clinical data, focusing on the EMERALD-1, LEAP-012 and EMERALD-3 clinical trials.

Results: EMERALD-1, a multicenter, phase III, randomized, double blinded, placebo-controlled study aimed to investigate TACE with Durvalumab or Durvalumab plus Bevacizumab against TACE alone for unresectable HCC. A significant benefit in progression free survival (PFS) was shown with Durvalumab plus Bevacizumab and TACE with a median PFS of 15 months compared to 8.2 months with placebo. LEAP-012, a multicenter, phase III, randomized, double-blinded and placebo-controlled study aimed to investigate TACE combined with Lenvatinib plus Pembrolizumab against TACE with placebo for unresectable non-metastatic HCC. Primary endpoints were PFS and overall survival (OS). In the TACE combined with Lenvatinib plus Pembrolizumab group median PFS was 14.6 months, while 24-month OS was 75%, compared to 10 months and 69% in the TACE with placebo group, respectively. EMERALD-3, a multicenter, phase III, randomized, open-label, sponsor-blinded study, with an expected primary completion in late 2025, aims to investigate Tremelimumab plus Durvalumab with or without Lenvatinib combined with TACE against TACE alone for patients with locoregional HCC.

Conclusions: TACE combined with immunotherapy has shown statistically significant improvement in primary endpoints in large phase-III trials. With additional data being collected in longer term analyses and the ongoing EMERALD-3 clinical trial, the landscape for HCC treatment will likely be significantly impacted in the near future.