Differential effects of prior versus concomitant Steroid and Antibiotic Treatment on Immunotherapy Efficacy - A Pooled Analysis of the RAMONA, INTEGA, OPTIM, ELDORANDO, FORCE, TITAN-RCC and TITAN-TCC Trials of the German AIO Study Group

BACKGROUND: We explored the association of immune-related adverse events (irAE), along with prior and concomitant antibiotic and steroid use, on oncological outcomes following immune checkpoint inhibitor (ICI) treatment in various solid tumours. METHODS: Pooled data from seven trials on ICI therapy across multiple cancer types (head and neck, non-small cell lung cancer, gastroesophageal junctional adenocarcinoma, oesophageal, renal cell, and urothelial carcinoma) was analysed, focusing on overall survival (OS) and progression-free survival (PFS) and antibiotic or steroid use before and during the study. RESULTS: Of 693 patients, 80 used steroids and 52 used antibiotics prior to the study, while 360 and 331, respectively, used them concomitantly. Lack of prior antibiotic use was associated with longer OS (No vs. Yes: HR 0.552, 95%-CI 0.370-0.822, p = 0.0035) and PFS (No vs. Yes: HR 0.703, 95%-CI 0.485-1.019, p = 0.0625), whereas concomitant antibiotic use had no such effect. Patients with concomitant steroid use demonstrated longer PFS (No vs. Yes: HR 1.359, 95%-CI 1.091-1.693, p = 0.0061). DISCUSSION: Our study confirmed associations between antibiotic and steroid use and ICI efficacy in cancer. Prior, but not concomitant, antibiotic use was linked to reduced OS, supporting the role of microbiome diversity in tumour response. Concomitant steroid use was associated with improved PFS, potentially reflecting its link to irAE occurrence.