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 Bishay; Dominik Bettinger; Max Sung; Celina Ang; Myron Schwartz; David J Pinato; Thomas Marron

doi:10.1136/jitc-2021-004205

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.

Authors

Brett Marinelli¹, Edward Kim¹, Antonio D'Alessio², Mario Cedillo¹, Ishan Sinha¹, Neha Debnath³, Masatoshi Kudo⁴, Naoshi Nishida⁴, Anwaar Saeed⁵, Hannah Hildebrand⁵, Ahmed O Kaseb⁶, Yehia I Abugabal⁶, Anjana Pillai⁷, Yi-Hsiang Huang^{8

9}, Uqba Khan¹⁰, Mahvish Muzaffar¹¹, Abdul Rafeh Naqash¹², Rahul Patel¹, Aaron Fischman¹, Vivian Bishay¹, Dominik Bettinger¹³, Max Sung³, Celina Ang¹⁴, Myron Schwartz¹⁵, David J Pinato², Thomas Marron¹⁶

Affiliations

¹ Division of Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
² Department of Surgery and Cancer, Imperial College London, London, UK.
³ Division of Hematology and Oncology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
⁴ Faculty of Medicine Hospital, Department of Gastroenterology and Hepatology, Kindai University, Osakasayama, Japan.
⁵ Department of Medicine, Division of Clinical Oncology, University of Kansas Medical Center, Kansas City, Kansas, USA.
⁶ Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁷ Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, Illinois, USA.
⁸ Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁹ Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.
¹⁰ Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York City, New York, USA.
¹¹ Department of Medicine, Division of Hematology and Oncology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
¹² Department of Medicine, Division of Hematology and Oncology, Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, Oklahoma, USA.
¹³ Department of Medicine II, University of Freiburg Medical Center, Freiburg, Germany.
¹⁴ Hematology and Oncology, Mount Sinai School of Medicine, New York City, New York, USA.
¹⁵ Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
¹⁶ Division of Hematology and Medical Oncology, Mount Sinai School of Medicine, New York City, New York, USA [email protected].

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