Antibiotics are associated with attenuated efficacy of anti-PD-1/PD-L1 therapies in Chinese patients with advanced non-small cell lung cancer

Abstract

Objectives: Gut microbiome plays a dominant role in modulating therapeutic efficacy of immune checkpoint inhibitors (ICIs) targeting the programmed cell death receptor/ligand-1 (PD-1/PD-L1) pathway, suggesting that co-administration of antibiotics (Abx), which might result in dysbacteriosis, can attenuate the clinical outcomes of ICIs. The current study aimed to investigate the predictive role of Abx on ICIs treatment in patients with advanced non-small cell lung cancer (NSCLC). The impact of proton pump inhibitors (PPIs), another medication that can induce dysbacteriosis, was also investigated.

Materials and methods: We retrospectively reviewed the medical records of eligible patients who received anti-PD-1-based therapies in our hospital. Tumor responses, patients' survival, the incidence of immune-related adverse events (irAEs) and other baseline variables were examined. The application of Abx or PPIs treatment were also collected. Clinical outcomes and clinicopathologic features were compared according to the status of Abx or PPIs co-administration.

Results: A total of 109 patients were included. Of them, 20 (18.3%) patients were categorized in Abx-treated group. No major difference in baseline characteristics was observed between Abx-treated and -untreated groups. Concomitant Abx treatment was significantly associated with shorter progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p = 0.0021). And primary disease progression tended to increase in Abx-treated group (p = 0.092). Yet, the occurrence and grades of irAEs were comparable between two groups. In multivariable analysis, Abx treatment was markedly associated with worse PFS (HR=0.32, 95%CI 0.18-0.59, p < 0.0001) and OS (HR=0.35, 95%CI 0.16-0.77, p = 0.009). Regarding the use of PPIs, no significant difference was observed in clinical outcomes between the patients with or without concomitant PPIs treatment.

Conclusions: Abx treatment was significantly associated with attenuated clinical outcomes derived from anti-PD-1-based ICIs in a Chinese cohort of patients with advanced NSCLC.

Keywords: Antibiotics; Immune checkpoint inhibitors; Non-small cell lung cancer; PD-1/PD-L1.