Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors.

Background

In patients with cirrhosis, portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, promoting an inflammatory state that can lead to the progression of liver disease and development of hepatocellular carcinoma (HCC). We aimed to investigate whether beta blockers (BBs), which can mediate portal hypertension, conferred survival benefits in patients treated with immune checkpoint inhibitors (ICIs).

Methods

We conducted a retrospective, observational study of 578 patients with unresectable HCC treated with ICI from 2017 to 2019 at 13 institutions across three continents. BB use was defined as exposure to BBs at any time during ICI therapy. The primary objective was to assess the association of BB exposure with overall survival (OS). Secondary objectives were to evaluate the association of BB use with progression-free survival (PFS) and objective response rate (ORR) according to RECIST 1.1 criteria.

Results

In our study cohort, 203 (35%) patients used BBs at any point during ICI therapy. Of these, 51% were taking a nonselective BB. BB use was not significantly correlated with OS (hazard ratio [HR] 1.12, 95% CI 0.9-1.39,

Conclusion

In this real-world population of patients with unresectable HCC treated with immunotherapy, BB use was not associated with OS, PFS or ORR.

Informations de copyright

Copyright © 2023 Wu, van Hyfte, Özbek, Reincke, Gampa, Mohamed, Nishida, Wietharn, Amara, Lee, Scheiner, Balcar, Pinter, Vogel, Weinmann, Saeed, Pillai, Rimassa, Naqash, Muzaffar, Huang, Kaseb, Kudo, Pinato and Ang.

Déclaration de conflit d'intérêts

UÖ is affiliated with Eli Lilly and Company. MR received lecture fees from Falk Foundation e.V. AV received consulting fees from Amgen, AstraZeneca, Baxalta, Bayer, BTG, EISA, Ipsen, Lilly, Novartis, Pierre Fabre, and Roche; travel fees from Bayer, Ipsen, and Roche; and research funding from Novartis. AS received lecture fees from Daiichi Sankyo/AstraZeneca; consulting fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo/ AstraZeneca, Exelixis, Five Prime Therapeutics, and Pfizer; and institutional funding from Actuate Therapeutics, Astellas Pharma, AstraZeneca/MedImmune, Bristol-Myers Squibb, Clovis Oncology, Daiichi Sankyo/UCB Japan; Exelixis, Fiver Prime Therapeutics, KAHR Medical, Merck Sharp & Dohme, and Seattle Genetics. AK received consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech/Roche, and Merck; travel fees from from Bayer/Onyx, Bristol-Myers Squibb, Exelixis, and Merck; and institutional research funding from Adaptimmune, Bayer/Onyx, Bristol-Myers Squibb, Genentech, Hengrui Pharmaceutical, and Merck. AP received consulting fees for Eisai Inc, Exelixis, AstraZeneca, Replimune and Genentech. LR received consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Bristol-Myers Squibb, Celgene, Eisai, Exelixis, Genenta Science, Hengrui Therapeutics, Incyte, Ipsen, IQvia, Lilly, Merck Sharp & Dohme, Nerviano Medical Sciences, Roche, Sanofi, Servier, Taiho Oncology, and Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi; travel fees from AstraZeneca; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, FibroGen, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Nerviano Medical Sciences, Roche, and Zymeworks. Y-HH received lecture fees from Bayer, Bristol-Myers Squibb, Eisai, Gilead Sciences, Lilly, MSD, and Roche; and consulting fees from Bayer, Bristol-Myers Squibb, Eisai, Gilead Sciences, Lilly, MSD, and Roche. DP received lecture fees from ViiV Healthcare, Bayer, Falk Pharma and Roche; travel expenses from Bristol-Myers Squibb, Bayer, and MSD Oncology; consulting fees for AstraZeneca, Da Volterra, EISAI, H3 Biomedicine, Ipsen, Mina Therapeutics, and Roche; and institutional research funding from Bristol-Myers Squibb, GlaxoSmithKline, and MSD Oncology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.