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Microbiome & Immunotherapy: Antibiotic Use Is Associated with Inferior Survival for Lung Cancer Patients Receiving PD-1 Inhibitors World Conference on Lung Cancer Abstract 693





Mounting evidence suggests the gut microbiome influences response to cancer immunotherapy. Antibiotic exposure (ATB+) alters the gut microbiome, and limited clinical data demonstrate ATB may negatively impact cancer immunotherapy response and survival outcomes. This study evaluates the impact of ATB+ on response and survival outcomes in patients with metastatic non-small-cell lung cancer (NSCLC) treated with programmed death-1 (PD-1) inhibitors.


We performed a retrospective review of all metastatic NSCLC patients treated with PD-1 inhibitors at our institution. A patient was considered to be in the ATB+ group if exposed to ATB within 6 weeks of initiating PD-1 inhibitors. All other patients were included in the antibiotic unexposed (ATB-) group. The primary outcome of interest was overall survival (OS), and secondary outcomes included overall response rate (ORR) and progression-free survival (PFS). ORR was compared between ATB+ and ATB- utilizing logistic regression modeling. The Kaplan-Meier method and Cox regression model were utilized to compare PFS and OS between ATB+ and ATB- groups.


A total of 74 patients met study eligibility criteria. The median age was 66 years old (range 33-88 years old). The majority of patients were male (55%), Caucasian (65%), and had adenocarcinoma histology (57%). A minority had brain metastases (15%) and radiation (38%) prior to receiving a PD-1 inhibitor. Most received nivolumab (95%). A total of 18 patients (24%) received antibiotics prior to initiating a PD-1 inhibitor, and most received fluoroquinolones (50%) for mild respiratory infections (72%). Antibiotic exposure did not impact ORR in our study. The ORR was 23% in ATB- and 25% in ATB+ patients (adjusted OR 1.2, p=0.20). ATB+ patients had inferior PFS compared to ATB- patients (median PFS 2.0 vs 3.8 months, p<0.001). Likewise, ATB+ patients had worse OS compared with ATB- (median OS 4.0 months vs 12.6 months, p=0.005). The association between ATB+ and inferior PFS (HR 2.5, p=0.02) and OS (HR 3.5, p=0.004) remained significant when controlling for age, sex, race, tobacco history, tumor histology, presence of brain metastases and previous radiation.


To our knowledge, this is the first study evaluating the impact of ATB on survival outcomes with immunotherapy in metastatic NSCLC. ATB+ was associated with inferior PFS and OS, suggesting a link between antibiotic-induced alteration of the gut microbiome and efficacy of immunotherapy. While this is a relatively small retrospective study, it does generate justification for further investigation into the interaction between the gut microbiome and cancer immunotherapy.

Author List

Jonathan R Thompson, Carlos Arce-Lara, Aniko Szabo, Smitha Menon


Jonathan R. Thompson MD Assistant Professor in the Medicine department at Medical College of Wisconsin
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