Early antibiotic exposure is not detrimental to therapeutic effect from immunotherapy in hepatocellular carcinoma
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background and Rationale: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC. Methods: In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within −30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. Results: Our study comprised mostly cirrhotic (329, 73.3%) males (355, 79.1%) with a Child-Turcotte Pugh class of A (332, 73.9%), receiving ICI after 1 therapy line (251, 55.9%) for HCC of Barcelona clinic liver cancer stage C (325, 72.4%). EIOP (n = 170, 37.9%) was independent of baseline clinicopathologic features of HCC and correlated with longer PFS (6.1 vs. 3.7 months, log-rank p = 0.0135). EIOP+ patients had similar OS, overall response, and disease control rates (DCRs) compared to EIOP. The effect of EIOP persisted in landmark time analyses and in multivariable models, confirming the independent predictive role of EIOP in influencing PFS following adjustment for covariates reflective of tumor burden, liver function, and ICI regimen administered. In patients receiving programmed cell death-1 receptor/ligand inhibitors monotherapy, EIOP was also associated with higher DCRs (61.4% vs. 50.9%, p = 0.0494). Conclusions: Unlike other oncological indications, ATB in the 30 days before or after ICI initiation is associated with improved benefit from immunotherapy, independent of disease and treatment-related features. Evaluation of the immune microbiologic determinants of response to ICI in HCC warrants further investigation.
Date Issued
2021-11-01
Date Acceptance
2021-07-19
Citation
Liver Cancer, 2021, 10 (6), pp.583-592
ISSN
2235-1795
Publisher
Karger Publishers
Start Page
583
End Page
592
Journal / Book Title
Liver Cancer
Volume
10
Issue
6
Copyright Statement
Published by S. Karger AG, Basel This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY) (http://www.karger.com/Services/ OpenAccessLicense). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34950181
PII: lic-0010-0583
Subjects
Antibiotics
Cancer immunotherapy
Gastroenterology & Hepatology
Gut microbiota
Hepatocellular carcinoma
Immune checkpoint inhibitors
Life Sciences & Biomedicine
Oncology
Science & Technology
Publication Status
Published
Coverage Spatial
Switzerland
Date Publish Online
2021-10-08