Tran, Dao2023-04-132023-04-132023-01https://hdl.handle.net/11299/253737University of Minnesota Ph.D. dissertation.January 2023. Major: Social and Administrative Pharmacy. Advisor: David Stenehjem. 1 computer file (PDF); xi, 215 pages.Background: In non-small cell lung cancer (NSCLC), only 20% of patients responded to immune checkpoint inhibitors (ICI). Patients with NSCLC often have infections which are treated with antibiotics. Corticosteroids are also used to treat NSCLC-related conditions. However, previous studies have suggested antibiotic and corticosteroid treatments reduce efficacy of ICI therapy. Using the SEER-Medicare linkage data, we examined baseline characteristics, antibiotic treatment patterns and overall survival in NSCLC patients treated with antibiotics and/or corticosteroids in the 30 days before or after ICI initiation. Methods: Patients with one diagnosis for lung cancer, and one histological code for NSCLC between 1/1/2011 and 6/30/2016 were selected. Subjects had 6+ months of continuous enrollment (CE) in Medicare Parts A, B, and D prior to the index ICI and 6+ months CE after to 12/31/2016 unless death occurred sooner. Treated (antibiotics or corticosteroids) patients had one or more claims for an antibiotic or corticosteroid during the 30 days before or 30 days after ICI initiation. Untreated patients had no claims for antibiotics or corticosteroids during the 30 days before or 30 days after ICI initiation. Overall survival (OS) was compared using Kaplan-Meier analyses. Results: Of 1,478 eligible patients, 38% received antibiotics, and 43% received corticosteroids in the 30 days before or after ICI. The mean (SD) age at ICI initiation was 73.51 (5.92) years. The mean (SD) Charlson comorbidity score was 5.1 (3.3). The most common antibiotic treatments were B-lactams (n=245, 43%) and fluoroquinolones (n=237, 42%). In the follow-up period, the median OS for antibiotic-treated vs. untreated patients was 8.3 months vs. 11.2 months (p=0.0003) and the corticosteroid-treated vs. untreated OS was 7.3 vs. 12.9 months (p<0.0001). The reduction in OS was most pronounced for patients treated with broad-spectrum anti-anaerobes (5.5 months, p=0.0063), other antibiotics (including vancomycin, nitrofurantoin, tobramycin, and sulfamethoxazole/trimethoprim) (4.1 months, p=0.0012), and 3rd & 4th generation cephalosporins (3.9 months, p=0.0191) than untreated. When compared to patients with no antibiotic and no corticosteroid, the OS was 4.7 months lower in patients with corticosteroids (13.1 vs. 8.4 months, p<0.0001) and 0.4 months lower in patients with antibiotics (13.1 vs. 12.7 months, p=0.288). When compared to those receiving both antibiotics and corticosteroids, the OS was 2.1 months longer for corticosteroids and no antibiotics (8.4 months vs. 6.3 months, p=0.015) and 6.4 months longer for antibiotics and no corticosteroids (12.7 months vs. 6.3 months, p<0.0001). Conclusions: Antibiotic and corticosteroid treatments are associated with shorter OS in NSCLC patients using ICIs. Broad-spectrum antibiotics have the most impact on OS, whereas penicillin, 1st and 2nd generation cephalosporins do not have a significant association with reduced OS. Future studies should control for clinical parameters such as performance measures and tumor mutation burden and they should explore progression-free survival to measure the impact of antibiotic and corticosteroid use on ICI therapy.enThesis or Dissertation