The Association Between Antibiotic Use and Outcome Among Metastatic Melanoma Patients Receiving Immunotherapy
Menée en France à partir de données de l'Assurance maladie portant sur des témoins et 2 605 patients atteints d'un mélanome de stade avancé et ayant reçu un traitement anti-PD-1 en première intention entre 2015 et 2017, cette étude analyse l'association entre une utilisation d'antibiotiques dans les 3 mois précédant le traitement et la survie globale ou le délai avant l'arrêt du traitement
Résumé en anglais
Several observational studies have reported a decreased response to immune checkpoint inhibitors (ICI) following antibiotic use. ICI activity has been hypothesized to be impaired by antibiotic-induced gut dysbiosis.Patients with advanced melanoma receiving an anti-PD-1 antibody as a first-line therapy between 2015 and 2017 in France were selected using the French Health Insurance database. We compared overall survival (OS) and time-to-treatment discontinuation (TTD) according to antibiotic exposure in the 3 months prior to the initiation of anti-PD-1 antibody. To disentangle a causal effect of antibiotics from a confounding bias, we balanced characteristics of patients exposed and non-exposed to antibiotics using an overlap weighting method based on a propensity score. We also evaluated a control cohort of patients with advanced melanoma receiving first-line targeted therapy, as there is no rationale for decreased efficacy of targeted therapy following antibiotic treatment.The anti-PD-1 antibody cohort comprised 2605 individuals. Antibiotic exposure in the 3 months prior to anti-PD-1 antibody initiation was not associated with shorter OS (weighted hazard ratio = 1.01, 95% confidence interval = 0.88–1.17) or TTD (weighted hazard ratio = 1.00, 95% confidence interval = 0.89–1.11). Consistent results were observed when the timeframe of antibiotics was narrowed to 1 month prior to anti-PD-1 initiation, or when exposure was restricted to antibiotics leading to more profound gut dysbiosis. Similar results were observed in the targeted therapy cohort.In a large cohort of advanced melanoma patients, we showed that antibiotic use preceding anti-PD-1 antibody was not associated with worse outcome. Physicians should not delay immunotherapy for patients who have recently received antibiotics.
