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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

Date

10/16/2017

Abstract

Background:

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.

Method:

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.

Result:

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.

Conclusion:

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

Author

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