Steroid and antibiotic treatment are associated with diverse immunotherapy efficacy a pooled analysis of the RAMONA, INTEGA, OPTIM, ELDORANDO, FORCE, TITAN-RCC and TITAN-TCC trials of the German AIO study group

Introduction: We explored the association between antibiotic and steroid use before or during immune checkpoint inhibitor (ICI) treatment, the occurrence of immune-related adverse events (irAE), and oncological outcomes in various solid tumors. Aims: We aimed to explore associations of immunotherapy efficacy and steroid and antibiotic medication. Methods: Pooled data from seven trials on ICI therapy across multiple cancer types (head and neck, non-small cell lung cancer, gastroesophageal junctional adenocarcinoma, esophageal, renal cell, and urothelial carcinoma) was analyzed, associating overall survival (OS) and progression-free survival (PFS), the occurrence of irAE, and the use of antibiotics or steroids before and during the respective studies. Results: Of 693 patients, 80 used steroids and 52 used antibiotics prior to the studies, while 360 and 331, respectively, used them concomitantly to ICI treatment. No prior antibiotic use positively affected OS (HR 0.659 [95%-CI 0.476;0.914], p=0.0124). No concomitant steroid use worsened PFS (HR 1.236 [95%-CI 1.014;1.507], p=0.0359) but had no effect on OS. Concomitant steroids were associated with multiple (p=0.0063) and serious irAE (p<0.0001), and with irAE of CTCAE grade ≥3 (p=0.0006) in multivariate logistic regression. Higher irAE rates were noted with concomitant use of steroids (No vs Yes: OR 0.529 [CI 0.369;0.759], p=0.0005) and antibiotics (no vs yes: OR 0.571 [95%-CI 0.399;0.815], p=0.0020). The occurrence of irAE was linked to better OS and PFS in univariate but not in multivariate analysis, indicating possible overlap with other factors. However, treatment duration was also a predictor of irAE (treatment duration ≤median vs > median: OR 0.525 [95%-CI 0.372; 0.743], p=0.0003). Conclusion: Our study identified links between antibiotic and steroid use and ICI efficacy in cancer. Steroid's impact on OS might be confounded by treatment duration, a notable predictor of irAE. Prior antibiotic use was associated with reduced OS, aligning with evidence that fecal microbiota transplantation before ICI therapy can enhance microbiome diversity and tumor response. Publication History Article published online: 26 September 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany