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.

摘要: BACKGROUND Some concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients 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 matter of debate. METHODS We present the outcomes analysis according baseline (prior ICI initiation) putative immune-modulatory effects a large cohort metastatic NSCLC PD-L1 ≥50%, receiving first-line pembrolizumab monotherapy. also evaluated control treated chemotherapy. The interaction between key therapeutic modality (pembrolizumab vs chemotherapy) was validated pooled multivariable analyses. RESULTS 950 595 were included chemotherapy cohorts, respectively. Corticosteroid proton pump inhibitor (PPI) therapy but not ATB poorer performance status at both cohorts. No association clinical found statin, aspirin, β-blocker metformin within cohort. On analysis, emerged as strong predictor overall (OS) (HR=1.42 (95% CI 1.13 1.79); p=0.0024), progression free (PFS) (HR=1.29 1.04 1.59); p=0.0192) Corticosteroids shorter PFS (HR=1.69 (95% CI 1.42 2.03); p<0.0001), OS (HR=1.93 1.59 2.35); p<0.0001) pembrolizumab, (HR=1.30 1.08 1.56), p=0.0046) (HR=1.58 1.29 1.94), PPIs (HR=1.49 1.26 1.77); (HR=1.12 1.02 1.24), p=0.0139), At there statistically significant for corticosteroids (p=0.0020) (p=0.0460) respect OS, (p<0.0001), (p=0.0290), (p=0.0487) PFS, only (p=0.0033) objective response rate. CONCLUSION In this study, we validate negative impact on monotherapy NSCLC, producing further evidence about their underlying effect. Even though magnitude significantly different across might be driven by adverse disease features.