Intestinal microbiota are important to control the systemic immune system. Antibiotics alter gut microbiota diversity and composition. Recent studies reported that the dysbiosis can lead to resistance to immune checkpoint inhibitors (ICI).
We examined 199 patients. They had NSCLC, melanoma, gastric, esophageal, RCC, bladder, and other cancers. Those receiving antibiotics within 30 days of beginning ICI were compared with those who did not. ICI were nivolumab (67.8%), pembrolizumab, and atezolizumab. We assessed objective response, and median overall survival (mOS). Only 118 patients were evaluated for response.
NSCLC was the most common with 58.7% (118 of 199). 57 of 199 (29%) received antibiotics within 30 days of beginning ICI. Antibiotics were commonly cephalosporins and most were used for more than 7 days. In response evaluation, antibiotic compared with no antibiotic was not associated progression (41% vs 50%, p = 0.66). In total patients, antibiotics showed shorter mOS (5vs14months, p = 0.002, HR 1.93 95% CI 1.2-3.0). In NSCLC, antibiotics had also shorter mOS (4vs17monts, p = 0.008, HR 2.1, 95%CI 1.2-3.7). Those receiving antibiotics 30 to 60 days before beginning ICI showed no difference in mOS (8vs17months, p = 0.224).
Antibiotics were associated with poor clinical outcomes from ICI in various cancer, especially NSCLC. Modulation of antibiotic-related changes of gut microbiota may be important to improve clinical outcomes in ICI for cancer treatment.
Clinical trial identification
Legal entity responsible for the study
The Catholic University of Korea, Seoul St. Mary\'s Hospital.
Has not received any funding.
All authors have declared no conflicts of interest.