Abstract 1413P
Background
Antibiotic therapy disrupts microbiota homeostasis, which is suggested to impair response to immune checkpoint blockade. We assessed whether antibiotic treatment predicts treatment outcomes of programmed death-1 (PD-1) inhibitors or chemotherapy in advanced gastric cancer (AGC).
Methods
Patients who were treated with PD-1 inhibitors (pembrolizumab or nivolumab; n=128) or irinotecan (n=93) between January 2017 and June 2020 in a tertiary referral center (Yonsei Cancer Center) were analyzed (primary cohort). Treatment outcomes were correlated with antibiotics usage. Another independent cohort treated with PD-1 blockade from tertiary referral center (Gangnam Severance Hospital) was analyzed for validation (secondary cohort; n=70).
Results
In the analysis of the primary cohort, prior antibiotic treatment (pATB; antibiotics usage within 28 days of treatment initiation) was associated with inferior response rate (P=0.001) and worse progression-free survival (HR=2.441, 95% CI=1.647-3.617) and overall survival (HR=1.913, 95% CI=1.301-2.813) in patients treated with PD-1 inhibitors. In contrast, there was no definite correlation between pATB and treatment outcomes of irinotecan. In the secondary cohort, treatment outcomes of PD-1 blockade were consistently worsened by pATB. Multivariate analysis for the overall patients treated with PD-1 blockade confirm that pATB was independently predicts worse PFS (HR=2.816, 95% CI=2.059-3.852) and OS (HR=2.174, 95% CI=1.599-2.957).
Conclusions
This study provided evidences that pATB is associated with inferior treatment response and survival outcomes in AGC patients treated with PD-1 inhibitors, suggesting that antibiotics-mediated changes in the landscape of micriobiota can be a therapeutically actionable target for patients who are planned to receive PD-1 inhibitors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.