Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy

作者：Alessio Cortellini, Massimo Di Maïo, Olga Nigro, Alessandro Leonetti, Diego Cortinovis, Joachim G.J.V. Aerts, Giorgia Guaitoli, Fausto Barbieri, Raffaele Giusti, Miriam Grazia Ferrara, Emilio Bria, Ettore D’Argento, Francesco Grossi, Erika Rijavec, Annalisa Guida, Rossana Berardi, Mariangela Torniai, Vincenzo Sforza, Carlo Genova, Francesca Mazzoni, Marina Chiara Garassino, Alessandro De Toma, Diego Signorelli, Alain Gelibter, Marco Siringo, Paolo Marchetti, Marianna Macerelli, Francesca Rastelli, Rita Chiari, Danilo Rocco, Luigi Della Gravara, Alessandro Inno, De Tursi Michele, Antonino Grassadonia, Pietro Di Marino, Giovanni Mansueto, Federica Zoratto, Marco Filetti, Daniele Santini, Fabrizio Citarella, Marco Russano, Luca Cantini, Alessandro Tuzi, Paola Bordi, Gabriele Minuti, Lorenza Landi, Serena Ricciardi, Maria Rita Migliorino, Francesco Passiglia, Paolo Bironzo, Giulio Metro, Vincenzo Adamo, Alessandro Russo, Gian Paolo Spinelli, Giuseppe Luigi Banna, Alex Friedlaender, Alfredo Addeo, Katia Cannita, Corrado Ficorella, Giampiero Porzio, David J. Pinato · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2021 · DOI：10.1136/jitc-2021-002421 · 被引用次数：152 · 研究领域：Cancer Immunotherapy and Biomarkers、Cancer, Lipids, and Metabolism、Inflammatory Biomarkers in Disease Prognosis

BACKGROUND: Some concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate. METHODS: We present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses. RESULTS: 950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS)...