Integrated use of PD-1 inhibition and transarterial chemoembolization for hepatocellular carcinoma : evaluation of safety and efficacy in a retrospective, propensity score-matched study
© 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..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Journal for immunotherapy of cancer - 10(2022), 6 vom: 16. Juni |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Marinelli, Brett [VerfasserIn] |
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| Links: |
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| Themen: |
31YO63LBSN |
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| Anmerkungen: |
Date Completed 20.06.2022 Date Revised 16.07.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1136/jitc-2021-004205 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Marinelli, Brett |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Integrated use of PD-1 inhibition and transarterial chemoembolization for hepatocellular carcinoma |b evaluation of safety and efficacy in a retrospective, propensity score-matched study |
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| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 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. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Combined Modality Therapy | |
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| 650 | 4 | |a Liver Neoplasms | |
| 650 | 7 | |a Programmed Cell Death 1 Receptor |2 NLM | |
| 650 | 7 | |a Nivolumab |2 NLM | |
| 650 | 7 | |a 31YO63LBSN |2 NLM | |
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| 700 | 1 | |a Naqash, Abdul Rafeh |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Rahul |e verfasserin |4 aut | |
| 700 | 1 | |a Fischman, Aaron |e verfasserin |4 aut | |
| 700 | 1 | |a Bishay, Vivian |e verfasserin |4 aut | |
| 700 | 1 | |a Bettinger, Dominik |e verfasserin |4 aut | |
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