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

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.

Informations de 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.

Déclaration de conflit d'intérêts

Competing interests: EK is a consultant for Koninklijke Philips Electronics (Amsterdam, Netherlands) and is on the advisory board for Onyx Pharmaceuticals (South San Francisco, California) and the speaker’s bureau for BTG International (West Conshohocken, Pennsylvania). RP is a consultant for Sirtex Medical (North Sydney, Australia) and Arstasis (Fremont, California). AF is a consultant for Surefire Medical (Westminster, Colorado) and Terumo Medical Corporation (Somerset, New Jersey) and is on the advisory board for Terumo Medical Corporation. DB is a consultant for Bayer Healthcare, Boston Scientific and Shionogi and lecturer for Falk Foundation. YH has research grants from Gilead Sciences and Bristol Myers Squibb and honoraria from Abbvie, Gilead Sciences, Bristol Myers Squibb, Ono Pharmaceutical, Merck Sharp & Dohme, Eisai, Eli Lilly, Ipsen and Roche, and serves as advisor for Abbvie, Gilead Sciences, Bristol Myers Squibb, Ono Pharmaceuticals, Eisai, Eli Lilly, Ipsen, Merck Sharp & Dohme and Roche. AS has research grants from AstraZeneca, Merck, Bristol Myers Squibb, Exelixis and Clovis and receives advisory board/consultant fees from AstraZeneca, Merck, Bristol Myers Squibb, Exelixis and Pfizer. AP is on the medical advisory board for Exelixis, Eisai, AstraZeneca and Genentech, safety review committee for Replimune and on the speaking bureau for Simply Speaking Hepatitis. MK is a consultant for Eisai, Ono Pharmaceutical Co, Merck Sharpe & Dohme Corp, Bristol Meyer Squibb and Roche; research contracts grants from Ono Pharmaceutical Co; grants from Eisai, Takeda, Otsuka, Taiho, EQ pharma, Gilead Sciences, Abbvie, Sumitomo Dainippon Pharma, Chugai, Ono Pharmaceutical; and is an honorary lecturer for Eisai, Bayer, Merck Sharpe & Dohme Corp, Bristol Meyer Squibb, EA Pharma, Eli Lilly and Chugai. TUM has served as an advisor and/or data-safety boards for Regeneron, Boehringer Ingelheim, Atara, Genentech, AstraZeneca, Chimeric Therapeutics, Riboscience, Celldex and Rockefeller University, and has research grants from Regeneron, Bristol-Myers Squibb and Boehringer Ingelheim. None of the other authors have identified a conflict of interest.