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Antibiotic Exposure Does Not Impact Anti-BRAF/Anti-MEK Targeted Therapy Outcome in Patients with Advanced Melanoma
Yu Shi Wang (Centre Hospitalier de l’Université de Montréal), Qing Yin Wang (Centre Hospitalier de l’Université de Montréal), Alexia Erika Moise (Centre Hospitalier de l’Université de Montréal), Hamida Claudia Syed (Centre Hospitalier de l’Université de Montréal), Julie Malo (Centre Hospitalier de l’Université de Montréal), Spencer Soberano (Centre Hospitalier de l’Université de Montréal), Wiam Belkaïd (Centre Hospitalier de l’Université de Montréal), Meriem Messaoudene (Centre Hospitalier de l’Université de Montréal), Karl Bélanger (Centre Hospitalier de l’Université de Montréal), Antoine Desîlets (Centre Hospitalier de l’Université de Montréal), Rahima Jamal (Centre Hospitalier de l’Université de Montréal), Bertrand Routy (Centre Hospitalier de l’Université de Montréal), Arielle Elkrief (Centre Hospitalier de l’Université de Montréal)
Abstract: The gut microbiome is an established predictor of response to immune checkpoint inhibitors (ICI) in melanoma, and antibiotic exposure prior to ICI initiation is a validated negative prognostic factor. About half of melanoma patients harbor BRAF mutations and are treated with BRAF/MEK inhibitors (BRAFi/MEKi). While the detrimental impact of antibiotics is well described in the ICI setting, their effect on BRAFi/MEKi efficacy remains unknown. We retrospectively analyzed 49 advanced BRAF-mutant melanoma patients treated with BRAFi/MEKi. Antibiotic-exposed patients were compared with non-exposed patients across three time windows: within 30, 60, or 90 days before and after therapy initiation. Outcomes included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). Among the cohort, 41% had antibiotic exposure within ±30 days, 53% within ±60 days, and 57% within ±90 days. Baseline characteristics were comparable between groups, except for worse ECOG scores in antibiotic-exposed patients. Across all windows, ORR, PFS, and OS were comparable between groups. Unlike what was observed in the ICI setting, antibiotic use did not negatively affect outcomes with BRAFi/MEKi. Despite small sample size, these findings suggest that the detrimental prognostic impact of antibiotics is specific to immunotherapy, highlighting the importance of evaluating the microbiome as a predictive biomarker across treatment contexts.