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Association of antibiotic treatment with survival outcomes in treatment-naïve melanoma patients receiving immune checkpoint blockade
Eleftheria Chorti (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung), Bernd Kowall (Institut für Medizinische Informatik, Biometrie und Epidemiologie, Essen University Hospital), Jessica C. Hassel (Heidelberg University, University Hospital Heidelberg), Bastian Schilling (Universitätsklinikum Würzburg), Michael Sachse (Klinikum Bremerhaven-Reinkenheide), Ralf Gutzmer (Medizinische Hochschule Hannover, Johannes Wesling Klinikum Minden), Carmen Loquai (University Medical Center of the Johannes Gutenberg University Mainz), Katharina Charlotte Kähler (University Hospital Schleswig-Holstein), Anika Hüsing (Institut für Medizinische Informatik, Biometrie und Epidemiologie, Essen University Hospital), Catharina Gilde (Medizinische Hochschule Hannover, Johannes Wesling Klinikum Minden), Carl Maximilian Thielmann (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung), Anne Zaremba (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung), Jan‐Malte Placke (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung), Emmanouil Gratsias (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung), Anna Martaki (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung), Alexander Roesch (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung), Selma Ugurel (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung), Dirk Schadendorf (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung), Elisabeth Livingstone (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung), Andreas Stang (Institut für Medizinische Informatik, Biometrie und Epidemiologie, Essen University Hospital), Lisa Zimmer (Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung)
Abstract: PURPOSE: The interaction of gut microbiome and immune system is being studied with increasing interest. Disturbing factors, such as antibiotics may impact the immune system via gut and interfere with tumor response to immune checkpoint blockade (ICB). METHODS: In this multicenter retrospective cohort study exclusively treatment-naïve patients with cutaneous or mucosal melanoma treated with first-line anti-PD-1 based ICB for advanced, non-resectable disease between 06/2013 and 09/2018 were included. Progression-free (PFS), and overall survival (OS) according to antibiotic exposure (within 60 days prior to ICB and after the start of ICB vs. no antibiotic exposure) were analyzed. To account for immortal time bias, data from patients with antibiotics during ICB were analyzed separately in the time periods before and after start of antibiotics. RESULTS: Among 578 patients with first-line anti-PD1 based ICB, 7% of patients received antibiotics within 60 days prior to ICB and 19% after starting ICB. Antibiotic exposure prior to ICB was associated with worse PFS (adjusted HR 1.75 [95% CI 1.22-2.52]) and OS (adjusted HR 1.64 [95% CI 1.04-2.58]) by multivariate analysis adjusting for potential confounders. The use of antibiotics after the start of ICB had no effect on either PFS (adjusted HR 1.19; 95% CI 0.89-1.60) or OS (adjusted HR 1.08; 95% CI 0.75-1.57). CONCLUSIONS: Antibiotic exposure within 60 days prior to ICB seems to be associated with worse PFS and OS in melanoma patients receiving first-line anti-PD1 based therapy, whereas antibiotics after the start of ICB do not appear to affect PFS or OS.