Arielle Elkrief1,2, Layal El Raichani3, Corentin Richard4, Meriem Messaoudene1, Wiam Belkaid1, Julie Malo1, Karl Belanger5, Wilson Miller2, Rahima Jamal5, Nathalie Letarte3, Philip Wong1,6, Bertrand Routy1,5. 1. Hematology and Oncology, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada. 2. Segal Cancer Center, Jewish General Hospital, Rossy Cancer Network, McGill University, Montreal, QC, Canada. 3. Department of Pharmacy, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada. 4. Oncology, Research Platform in Biological Oncology, Dijon, France. 5. Hematology-Oncology Division, Department of Medicine, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada. 6. Division of radiation oncology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada.
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.
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.
Entities:
Keywords:
Melanoma; antibiotics; dysbiosis; gut microbiome; immune check-point inhibition; immunotherapy
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