Liver Cancer (Oct 2021)

Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma

  • Petros Fessas,
  • Muntaha Naeem,
  • Matthias Pinter,
  • Thomas U. Marron,
  • David Szafron,
  • Lorenz Balcar,
  • Anwaar Saeed,
  • Tomi Jun,
  • Sirish Dharmapuri,
  • Anuhya Gampa,
  • Yinghong Wang,
  • Uqba Khan,
  • Mahvish Muzaffar,
  • Musharraf Navaid,
  • Pei-Chang Lee,
  • Anushi Bulumulle,
  • Bo Yu,
  • Sonal Paul,
  • Neil Nimkar,
  • Dominik Bettinger,
  • Hannah Hildebrand,
  • Yehia I. Abugabal,
  • Tiziana Pressiani,
  • Nicola Personeni,
  • Naoshi Nishida,
  • Masatoshi Kudo,
  • Ahmed Kaseb,
  • Yi-Hsiang Huang,
  • Celina Ang,
  • Anjana Pillai,
  • Lorenza Rimassa,
  • Abdul Rafeh Naqash,
  • Elad Sharon,
  • Alessio Cortellini,
  • David J. Pinato

DOI
https://doi.org/10.1159/000519108
Journal volume & issue
Vol. 10, no. 6
pp. 583 – 592

Abstract

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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.

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