Open AccessEarly Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma
Author(s) -
Fessas Petros,
Naeem Muntaha,
Pinter Matthias,
Marron Thomas U.,
Szafron David,
Balcar Lorenz,
Saeed Anwaar,
Jun Tomi,
Dharmapuri Sirish,
Gampa Anuhya,
Wang Yinghong,
Khan Uqba,
Muzaffar Mahvish,
Navaid Musharraf,
Lee Pei-Chang,
Bulumulle Anushi,
Yu Bo,
Paul Sonal,
Nimkar Neil,
Bettinger Dominik,
Hildebrand Hannah,
Abugabal Yehia I.,
Pressiani Tiziana,
Personeni Nicola,
Nishida Naoshi,
Kudo Masatoshi,
Kaseb Ahmed,
Huang Yi-Hsiang,
Ang Celina,
Pillai Anjana,
Rimassa Lorenza,
Naqash Abdul Rafeh,
Sharon Elad,
Cortellini Alessio,
Pinato David J.
Publication year - 2021
Publication title -
liver cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.916
H-Index - 34
eISSN - 1664-5553
pISSN - 2235-1795
DOI - 10.1159/000519108
Subject(s) - research article
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.