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

J Immunother Cancer. 2022 Jun;10(6):e004205. doi: 10.1136/jitc-2021-004205.

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.

Keywords: Combined Modality Therapy; Immunomodulation; Liver Neoplasms.

Publication types

  • Multicenter Study

MeSH terms

  • 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

Substances

  • Programmed Cell Death 1 Receptor
  • Nivolumab