Abstract 1577P
Background
Antibiotic therapy has been known to disrupt microbiota homeostasis and systemic immune responses, both of which are linked to response to immune checkpoint blockade. We aim to investigate whether prior antibiotics (pATB) administration influences outcomes following treatment with programmed cell death protein-1 (PD-1) inhibitors or chemotherapy in patients with advanced gastric cancer (AGC).
Methods
We analysed data of patients with AGC who were treated with PD-1 inhibitors (retrospective exploratory cohort; n=152) or irinotecan (chemotherapy cohort; n=101). Patients were classified into two groups based on whether they had received pATB within 28 days prior to the treatment. Another independent retrospective validation cohort (n=123) and prospective validation cohort (n=30) treated with PD-1 inhibitors were further analysed. Distinct features in gut microbiome and circulating immune cells were analysed (experimental cohort; n=24).
Results
In the retrospective exploratory cohort, pATB administration was associated with poor 17 progression-free survival (PFS; hazard ratio [HR]=2.897, 95% confidence interval [CI]=2.043–4.109) and overall survival (OS; HR=2.294, 95% CI=1.622–3.242) but did not affect outcomes among patients treated with irinotecan. In the validation cohorts, pATB administration was associated with poor treatment outcomes following PD-1 blockade. Multivariate analysis of the overall patients treated with PD-1 inhibitors confirmed that pATB was an independent predictor of poor PFS (HR=3.243, 95% CI=2.427–4.333) and OS (HR=3.046, 95% CI= 2.358–3.935). Administration of pATB was associated with diminished gut microbiome diversity, reduced abundance of Lactobacillus gasseri, and disproportional enrichment of circulating exhaustive CD8+ T cells, all of which can hinder the efficacy of PD-1 blockade.
Conclusions
Considering the inferior treatment response and poor survival outcomes by pATB followed by PD-1 blockade, antibiotics should be prescribed with caution in patients with AGC planned to receive PD-1 inhibitors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Research Foundation of Korea, Ministry of Science and ICT, Yonsei University College of Medicine.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1580P - Early onset oesophageal adenocarcinoma: A separate biological entity?
Presenter: Dharmesh Valand
Session: Poster session 22
1581P - Total neoadjuvant chemotherapy with FOLFIRINOX regimen in patients with resectable locally advanced gastric and gastroesophageal junction cancer
Presenter: Maria Sedova
Session: Poster session 22
1582P - Gastroesophageal adenocarcinoma in young adults: Retrospective analysis of clinical and molecular features
Presenter: Daniel Acosta Eyzaguirre
Session: Poster session 22
1583P - Intraperitoneal chemotherapy for peritoneal metastases of gastric origin: A systematic review and meta-analysis
Presenter: Niels Guchelaar
Session: Poster session 22
1585P - The impact of platinum-induced peripheral neuropathy (PN) in first-line treatment on PN and efficacy in second-line paclitaxel (PTX)-based chemotherapy for unresectable advanced gastric cancer (AGC): A prospective observational multicenter study - IVY study
Presenter: Yoshiyasu Kono
Session: Poster session 22
1587P - Analysis of survival outcomes according to start timing of adjuvant chemotherapy in patients with gastric cancer: A retrospective nationwide cohort study
Presenter: Tae-Hwan Kim
Session: Poster session 22
1588P - Analysis of risk factors of anastomotic leakage after minimally invasive esophagectomy with circular cervical anastomosis
Presenter: ming lu
Session: Poster session 22
1589P - Systemic treatment strategies and outcomes of patients with peritoneal metastases of gastric origin
Presenter: Niels Guchelaar
Session: Poster session 22