Impact of antibiotic treatment on immune-checkpoint blockade efficacy in advanced non-squamous non-small cell lung cancer
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Florian Huemer1,*, Gabriel Rinnerthaler1,*, Theresa Westphal1, Hubert Hackl4, Georg Hutarew5, Simon Peter Gampenrieder1, Lukas Weiss1 and Richard Greil1,2,3
1IIIrd Medical Department, Paracelsus Medical University Salzburg, Salzburg, Austria
2Salzburg Cancer Research Institute (SCRI), Salzburg, Austria
3Cancer Cluster Salzburg (CCS), Salzburg, Austria
4Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
5Institute of Pathology, Paracelsus Medical University Salzburg, Salzburg, Austria
*These authors have contributed equally to this work
Richard Greil, email: [email protected]
Keywords: immune-checkpoint blockade; antibiotics; non-squamous non-small cell lung cancer; progression-free survival; overall survival
Received: October 19, 2017 Accepted: March 05, 2018 Published: March 27, 2018
Introduction: Despite durable responses from immune-checkpoint blockade (ICB) in a subset of patients with advanced non-small cell lung cancer (NSCLC), the majority of patients do not derive benefit from this treatment. In this analysis we evaluated the impact of concomitant administration of antibiotics during initiation of ICB on clinical outcome.
Methods: Advanced non-squamous NSCLC patients receiving ICB as second- or later line between 2015 and 2017 at our tertiary cancer center in Salzburg (Austria) were included. Concomitant use of antibiotics was defined as administration of antibiotics within a time frame of one month before or one month after initiation of ICB (AB+-group).
Results: Of the 30 patients included, 11 (36.7%) received antibiotics one month before or one month after start of ICB (AB+-group). Median PFS on ICB was in favor of the AB--group (AB-: 3.1 months [95%CI: 3.0-16.3]; AB+: 2.9 months, [95%CI: 1.9-NA]; HR=0.46 [95%CI: 0.12-0.90], p=0.031). Furthermore, median OS was significantly longer in the AB--group (AB-: 15.1 months [95%CI: 11.1-NA]; AB+: 7.5 months [95%CI: 6.3-NA]; HR=0.31 [95%CI: 0.02-0.78], p=0.026). In a multivariate analysis, the antibiotic treatment status was identified as the only parameter statistically significantly associated with PFS (p=0.028) and OS (p=0.026).
Conclusions: Stratification of patients according to the antibiotic treatment status is warranted in future trials investigating ICB.
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