Integrated use of PD-1 inhibition and transarterial chemoembolization for hepatocellular carcinoma: evaluation of safety and efficacy in a retrospective, propensity score-matched study

Brett Marinelli, Edward Kim, Antonio D'Alessio, Mario Cedillo, Ishan Sinha, Neha Debnath, Masatoshi Kudo, Naoshi Nishida, Anwaar Saeed, Hannah Hildebrand, Ahmed O. Kaseb, Yehia I. Abugabal, Anjana Pillai, Yi Hsiang Huang, Uqba Khan, Mahvish Muzaffar, Abdul Rafeh Naqash, Rahul Patel, Aaron Fischman, Vivian BishayDominik Bettinger, Max Sung, Celina Ang, Myron Schwartz, David J. Pinato, Thomas Marron

Research output: Contribution to journalArticlepeer-review

Abstract

Background Immune checkpoint inhibitors (ICIs) have revolutionized treatment of advanced hepatocellular carcinoma. Integrated use of transarterial chemoembolization (TACE), a locoregional inducer of immunogenic cell death, with ICI has not been formally assessed for safety and efficacy outcomes. Methods From a retrospective multicenter dataset of 323 patients treated with ICI, we identified 31 patients who underwent >1 TACE 60 days before or concurrently, with nivolumab at a single center. We derived a propensity score-matched cohort of 104 patients based on Child-Pugh Score, portal vein thrombosis, extrahepatic metastasis and alpha fetoprotein (AFP) who received nivolumab monotherapy. We described overall survival (OS), progression-free survival (PFS), objective responses according to modified RECIST criteria and safety in the multimodal arm in comparison to monotherapy. Results Over a median follow-up of 9.3 (IQR 4.0-16.4) months, patients undergoing multimodal immunotherapy with TACE achieved a significantly longer median (95% CI) PFS of 8.8 (6.2-23.2) vs 3.7 (2.7-5.4) months (log-rank 0.15, p<0.01) in the monotherapy group. Multimodal immunotherapy with TACE demonstrated a numerically longer OS compared with ICI monotherapy with a median 35.1 (16.1-Not Evaluable) vs 16.6 (15.7-32.6) months (log-rank 0.41, p=0.12). In the multimodal treatment group, there were three (10%) grade 3 or higher adverse events (AEs) attributed to immunotherapy compared with seven (6.7%) in the matched ICI monotherapy arm. There were no AEs grade 3 or higher attributed to TACE in the multimodal treatment arm. At 3 months following each TACE in the multimodal arm, there was an overall objective response rate of 84%. There were no significant changes in liver functional reserve 1 month following each TACE. Four patients undergoing multimodal treatment were successfully bridged to transplant. Conclusions TACE can be safely integrated with programmed cell death 1 blockade and may lead to a significant delay in tumor progression and disease downstaging in selected patients.

Original languageEnglish
Article numbere004205
JournalJournal for ImmunoTherapy of Cancer
Volume10
Issue number6
DOIs
StatePublished - 16 Jun 2022

Keywords

  • Combined Modality Therapy
  • Immunomodulation
  • Liver Neoplasms

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