Aims
While preclinical data demonstrates an association between the gut microbiome and response to immune checkpoint inhibitors (ICI), there is limited clinical data around the impact of concomitant medicines known to affect the gut microbiome, such as antibiotics. This study retrospectively assessed overall survival (OS) and treatment duration among patients treated with ICI for melanoma, with or without concomitant antibiotic use.
Methods
Patients who received the first ICI dose between August 2012 and May 2018 were identified using the Melanoma Research Victoria Project. Demographic, diagnostic, treatment and outcomes data were linked to Pharmaceutical Benefits Scheme (PBS) data for timing, type and duration of antibiotic therapy. Treatment duration and OS were analysed from date of first dose ICI and also according to the use of antibiotics within 30days of the first ICI dose, any ICI dose and cumulative days at any ICI dose.
Results
During the analysis period 121 patients commenced ICI therapy, of which 17% received antibiotics within 30days of the first ICI dose, 40% within 30days of any ICI dose, and 25% received more than 10days cumulative antibiotic treatment within 30days of any ICI dose. At analysis, 15% of the cohort were deceased and 46% had ceased ICI therapy. While survival data is immature, separation of survival curves and a non-significant trend for adverse survival outcomes was observed with antibiotic use within 30days of first ICI dose (1.70, 95%CI, 0.59-4.99), but not for subsequent doses or cumulative use. Antibiotic use did not appear to affect duration of ICI therapy.
Conclusion
Antibiotic use during ICI therapy is common with uncertain clinical impact. Analysis in larger, more mature cohorts is required to facilitate definitive conclusions.