Antibiotics are associated with decreased progression-free survival of advanced melanoma patients treated with immune checkpoint inhibitors

Abstract

Background: The gut microbiota has been shown to be an important determinant of the efficacy of immune checkpoint inhibitions (ICI) in cancer. Several lines of evidence suggest that antibiotic (ATB) usage prior to or within the first month of ICI initiation negatively impacts clinical outcomes. Methods: We examined patients with advanced melanoma treated with an anti-PD-1 monoclonal antibody (mAb) or an anti-CTLA-4 mAb alone or in combination with chemotherapy. Those receiving ATB within 30 days of beginning ICI were compared with those who did not receive ATB. Response rates as determined by RECIST 1.1, progression-free survival (PFS), overall survival (OS) and immune-related toxicities were assessed. Results: Of these 74 patients analyzed, a total of 10 patients received ATB (13.5%) within 30 days of initiation of ICI. Patients who received ATB 30 days prior to the administration of ICI experienced more primary resistance (progressive disease) (0% of the objective response rate compared to 34%), and progression-free survival (PFS) was significantly shorter (2.4 vs 7.3 months, HR 0.28, 95% CI (0.10–0.76) p = 0.01). Overall survival (OS) was also shorter; however, this was not statistically significant (10.7 vs 18.3 months, HR:0.52, 95% CI (0.21–1.32) p = 0.17). The multivariate analysis further supported that ATB administration was associated with worse PFS (HR 0.32 (0.13–0.83) 95% CI, p = 0.02). Conclusion: These findings suggest that ATB use within 30 days prior to ICI initiation in patients with advanced melanoma may adversely affect patient outcomes.

Keywords

• melanoma
• immunotherapy
• immune check-point inhibition
• antibiotics
• gut microbiome
• dysbiosis