Concomitant medication use and clinical outcome in hepatocellular carcinoma treated with immune-based therapy: a multicenter analysis.

INTRODUCTION

Immune checkpoint inhibitors (ICIs) have been increasingly used in hepatocellular carcinoma (HCC). Despite emerging evidence indicating that concomitant medications might impact clinical outcomes, their association with ICI efficacy is undefined in HCC.

METHODS

The multicenter cohort included 851 HCC patients receiving ICIs between January 2018 and December 2022 in 13 institutions. Concomitant medications given within 30 days before or after the initiation of ICIs were evaluated in association with survival, tumor response, and treatment-related adverse event (TRAE) occurrence. Concomitant medications administered within 30 days before or after the initiation of ICI therapy were identified and used to categorize patients into user and non-user groups for each medication class. The primary outcomes were overall survival (OS), and secondary outcomes included progression-free survival (PFS), time to progression (TTP), tumor response, and TRAEs. Tumor response was evaluated based on RECIST 1.1. Multivariable Cox and logistic regression models were used to adjust for confounding variables.

RESULTS

The median OS (13.6 vs. 20.7 months; P = 0.006) and PFS (6.6 vs. 8.9 months; P = 0.002) were significantly reduced for antibiotic users compared to non-users, while other drugs did not show an impact on patient outcomes. In multivariable analysis, antibiotic use predicted worse survival outcomes (OS: HR = 1.88, 95% CI, 1.14-3.11; P = 0.014; PFS: HR = 1.60, 95% CI, 1.20-2.13; P = 0.001). Patients who underwent glucocorticoids for early TRAE management achieved longer OS than those for prophylactic use (OS: Not reached vs. 20.3 months; HR = 0.25, 95% CI, 0.10-0.65; P = 0.042). Concomitant use of medications such as antibiotics, H2RAs, and glucocorticoids was associated with increased incidence of specific TRAEs, particularly involving hematologic, hepatic, and endocrine systems.

CONCLUSION

This study identified antibiotic use as a negative prognostic factor in HCC treated with ICIs, while glucocorticoid for early TRAEs may indicate improved survival benefits. Concomitant medication may affect the occurrence of TRAEs and warrants careful consideration during ICI treatment.