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. 2025 Mar 3;9(2):pkaf024.
doi: 10.1093/jncics/pkaf024.

Antibiotic treatment and survival in patients with resected, early-stage pancreatic ductal adenocarcinoma receiving chemotherapy

Emma Gong  1 , Daniel J Fulop  2 , Joyce Serebrenik  1 , Arielle J Labiner  3 , Deirdre J Cohen  4 , Keith M Sigel  5 , Aimee L Lucas  1
Affiliations

Antibiotic treatment and survival in patients with resected, early-stage pancreatic ductal adenocarcinoma receiving chemotherapy

Emma Gong et al. JNCI Cancer Spectr. .

Abstract

Background: Pancreatic ductal adenocarcinoma is a clinically challenging malignancy largely because of its chemoresistance. Bacteria within the pancreatic ductal adenocarcinoma microbiome may mediate chemoresistance, suggesting that alteration of the microbiome with antibiotics could improve chemotherapy response.

Methods: We utilized the Surveillance, Epidemiology, and End Results Program-Medicare database to select patients with resected, early-stage pancreatic ductal adenocarcinoma diagnosed between 2007 and 2017. The primary outcome of this study was overall survival. Receipt of antibiotic treatment within 1 month after adjuvant chemotherapy initiation was determined from Medicare claims data. Propensity scores were used to match patients who received antibiotics with patients who did not receive antibiotics. The Kaplan-Meier method was used to calculate 5-year overall survival rates, and Cox regression analysis was used to assess the association between receiving antibiotics and overall survival. All hypotheses were 2 sided.

Results: Of the 712 patients with resected, early-stage pancreatic ductal adenocarcinoma, 629 (88.3%) were treated with adjuvant gemcitabine and 177 (24.9%) received antibiotics in the 1 month following chemotherapy initiation. The mean (SD) age at diagnosis was 73.7 (5.1) years, and patients were mostly women, White, and from metropolitan areas in the northeastern or western United States. A total of 143 propensity score-matched pairs were evaluated. Among patients treated with gemcitabine, antibiotic treatment was associated with a 37% improvement in overall survival and a 30% improvement in cancer-specific survival.

Conclusions: Antibiotic treatment in the 1 month following adjuvant gemcitabine initiation was associated with improved survival. These findings provide additional support for the hypothesis that antibiotic treatment may alter the pancreatic microbiome in a manner that reduces chemoresistance, potentially improving pancreatic ductal adenocarcinoma outcomes.

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Conflict of interest statement

Ms Gong reported receiving grants from the Digestive Disease Research Foundation during the conduct of the study. Dr Cohen reported receiving grants and consulting fees from Astellas Pharma US, Inc; Guardant; Loxo@Lilly; and Seagen outside the submitted work. Dr Lucas reported receiving grants and consulting fees from Immunovia, Aionco, and ClearNote Health as well as royalties from UpToDate outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.
Full and propensity score–matched cohort. Abbreviation: SEER = Surveillance, Epidemiology, and End Results.
Figure 2.
Figure 2.
Association of antibiotic receipt with overall survival in a propensity score–matched cohort. Five-year survival for patients who did and did not receive antibiotics during the exposure period, 1 month after initiation of chemotherapy. In the full propensity score–matched cohort (A), median survival with antibiotics was 23.9 months (95% CI = 20.4 to 27.1 months) and with no antibiotics was 18.2 months (95% CI = 15.9 to 20.9 months) (log rank P = .001). In the gemcitabine cohort (B), median survival with antibiotics was 24.3 months (95% CI = 20.8 to 27.9 months) and with no antibiotics was 20.0 months (95% CI = 17.3 to 21.6 months) (log rank P = .001). * Masking to protect patient anonymity due to small differences by subtraction to adjacent numbers at risk.
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