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

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2019-04, Vol.130, p.10-17
• Main Authors: Zhao, Sha, Gao, Guanghui, Li, Wei, Li, Xuefei, Zhao, Chao, Jiang, Tao, Jia, Yijun, He, Yayi, Li, Aiwu, Su, Chunxia, Ren, Shengxiang, Chen, Xiaoxia, Zhou, Caicun
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - epidemiology; Carcinoma, Non-Small-Cell Lung - mortality; China - epidemiology; Drug Therapy, Combination; Dysbiosis - drug therapy; Dysbiosis - epidemiology; Female; Humans; Immune checkpoint inhibitors; Immunotherapy - methods; Lung Neoplasms - drug therapy; Lung Neoplasms - epidemiology; Lung Neoplasms - mortality; Male; Middle Aged; Non-small cell lung cancer; PD-1/PD-L1; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Retrospective Studies; Survival Analysis
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2019.01.017

•The efficacy of ICIs varies among NSCLC patients who have received Abx treatment or not.•Concomitant Abx treatment is correlated with worse survival benefits from ICIs therapies.•Concomitant Abx treatment is not associated with the occurrence and grades of irAEs. 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. 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. 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