Antibiotic exposure around first line chemotherapy and survival in ovarian cancer (347)

Abstract

<b>Objectives:</b> To assess whether exposure to antibiotics (ABX) in the 90 days preceding initiation through the completion of first-line chemotherapy for epithelial ovarian carcinoma (EOC) is associated with decreased overall survival (OS) and truncated treatment-free interval (TFI), which we hypothesized. <b>Methods:</b> A retrospective cohort study of women with newly diagnosed stage III/IV EOC between 2009 to 2019 treated at a single institution was conducted. ABX exposure of >48 hours, timing with respect to chemotherapy initiation, and ABX class were captured. The association of ABX with TFI and OS was assessed with univariate and multivariable Cox proportional hazard models. <b>Results:</b> Of the 360 eligible women, 47% (<i>n</i>=170) were exposed to antibiotics, with 12% (<i>n</i>=46) receiving them only prior to first-line chemotherapy initiation, 23% (<i>n</i>=81) receiving them during chemotherapy, and 12% (<i>n</i>=43) receiving them before and during chemotherapy. Exposure to any ABX was associated with a decreased median OS (42.1 vs 60.0 months, HR: 1.33, 95% CI: 1.02-1.73, p=0.03) compared to no ABX. On subset analyses, ABX, specifically during chemotherapy, was associated with a decreased median OS (42.2 vs 60.0 months, HR: 1.46, 95% CI: 1.01-2.10). While exposure to ABX as a whole was not associated with TFI, receipt of ABX before chemotherapy was associated with a decreased TFI, with an HR of 1.76 (95% CI: 1.00-3.11, p=0.05), when compared to no ABX. Treatment with antibiotics against gram-positive organisms (GPO) with vancomycin, lin- cosamides, and macrolides was associated with worse OS (HR: 1.49, 95% CI: 1.01-2.20, p=0.049). In a multivariable analysis accounting for bowel surgery, exposure to granulocyte colony-stimulating factor, and IP chemo administration, exposure to ABX remained associated with an increased risk of death (HR: 1.38, 95% CI: 1.02-1.68, p=0.039). <b>Conclusions:</b> Patients with stage III/IV EOC exposed to ABX 90 days prior to chemotherapy had statistically significantly worse TFI compared to unexposed patients. In contrast, patients exposed to ABX during chemotherapy had worse OS compared to unexposed patients. Treatment with ABX targeting GPO decreased OS. Efforts to decrease the need for ABX, such as judicious prescription of ABX and implementation of perioperative infection prevention bundles, may offer an opportunity to increase survival in EOC.