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

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.

• Authors: 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 Bishay, Dominik Bettinger, Max Sung, Celina Ang, Myron Schwartz, David J Pinato, Thomas Marron
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 10 Issue 6 (06 2022) ISSN: 2051-1426 [Electronic] England
• PMID: 35710293 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Programmed Cell Death 1 Receptor
• Nivolumab

Topics

• Carcinoma, Hepatocellular (drug therapy)
• Chemoembolization, Therapeutic (adverse effects)
• Humans
• Liver Neoplasms (pathology)
• Nivolumab (therapeutic use)
• Programmed Cell Death 1 Receptor
• Propensity Score
• Retrospective Studies
• Treatment Outcome