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Abstract: e14141 Background: Pre clinical studies have demonstrated the effect of gut microbiome in the efficacy of immune check point inhibitors. The effect of antibiotic exposure to patients receiving PD-1/CTLA-4 inhibitor therapy has not been extensively studied, especially in metastatic melanoma. In this study, we demonstrate the effect of antibiotic exposure to metastatic melanoma patients receiving PD-1/CTLA-4 inhibitor therapy. Methods: We performed a retrospective analysis of 108 patients with stage 4 metastatic melanoma who received immunotherapy with PD-1 inhibitors or CTLA-4 inhibitors or combination of both between Nov 2010 and Oct 2017. Patients were divided into Abx(+) and Abx(-) groups that were defined as patients exposed or not exposed to antibiotics respectively. The time frame for antibiotic exposure was taken from 6 months prior to 1 month after initiation of immunotherapy. We compared progression free survival (PFS), overall survival (OS) and response rate (RR) between the two groups. RR was calculated based on the entire length of follow-up. PFS and OS were assessed using Kaplan-Meier estimates. Cox proportional hazards were used to calculate hazard ratios. Results: Out of 108 patients, 66 (61.1%) were men, with a mean age 64.6 ± 15.1 years. 46 (42.6%) patients were exposed to antibiotics of varied classes. Median PFS in abx(+) group [88 days (95%CI: 70, 104)] was shorter as compared to abx(-) group [322 days (95%CI: 191, 410), p < 0.0001)]. Patients in abx(-) group had a 68% (95%CI: 45, 82) reduced risk of progression within 200 days of immunotherapy initiation adjusting for sex, age and number of immunotherapy cycles (p < 0.0001) . Median OS in ab(+) group [294 days (95%CI: 198, 345)] was shorter as compared to abx(-) group [573 days (95%CI: 453, 677)], p < 0.0001. Response rate defined as percentage of patients whose cancer was stable or entered remission was 12.9% (95%CI: 5.7, 23.9) in abx(-) group as compared to 8.7% (95%CI: 2.4, 20.8) ab(+) group. Patients in abx(-) group had a 52% (95% CI: 24, 69) reduced risk of death adjusting for sex, age and number of immunotherapy cycles (p = 0.002). Conclusions: Antibiotic exposure is associated with poorer outcomes in patients with advanced metastatic melanoma being treated with PD-1/CTLA-4 inhibitors which is likely related to alteration of gut microbiome. Antibiotics should be prescribed with caution in patients undergoing treatment with immune check point inhibitors. These data should be validated in a larger patient population.