Early antibiotic exposure, but not late exposure, negatively affects the clinical outcomes of first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma

The influence of antibiotic (ATB) exposure on the therapeutic efficacy of immunotherapy remains unclear for unresectable hepatocellular carcinoma (uHCC). This study aims to investigate the impact of early and late ATB exposure during atezolizumab plus bevacizumab (atezo/bev) therapy on progression-free survival (PFS) and overall survival (OS) in uHCC patients. In this retrospective cohort study, patients with uHCC receiving atezo/bev as first-line therapy between August 2020 and December 2022 were analyzed. We defined early ATB exposure as within 30 days of atezo/bev initiaion and late ATB exposure as within 30 days before each atezo/bev cycle, except the initial one. We used propensity score (PS) matching at a 1:2 ratio for covariates. A total of 177 uHCC patients were analyzed. Early ATB exposure was associated with significantly shorter PFS (2.3 vs. 6.3 months, Log rank p = 0.025; HR 1.92, p = 0.025) and OS (5.8 vs. 16.9 months, Log rank p = 0.0016; HR 2.30, p = 0.019). Similar results were observed in PS-matched analyses of PFS and OS. Late ATB exposure, in comparison to no ATB exposure, showed comparable PFS (6.1 vs. 6.5 months, Log rank p = 0.60; HR 0.74, p = 0.39) and OS (8.2 vs. 16.9 months, Log rank p = 0.31; HR 1.06, p = 0.89). In addition, late ATB exposure was associated with longer PFS and OS compared to early ATB exposure. Early ATB exposure, but not late exposure, is linked to inferior PFS and OS in uHCC patients undergoing first-line atezo/bev therapy. This study suggests a cautious approach to antibiotic use in these patients.