1067P - 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

Background

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.

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).

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

I. Wiest: Financial Interests, Personal, Invited Speaker: AstraZeneca. M. Marin-Galiano: Financial Interests, Personal, Other, Employee (Senior Statistician): M.A.R.C.O. GmbH & Co. KG. M.J. Grimm: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, EUSA Pharma, Gilead, Ipsen Pharma, Janssen Cilag, Merck Serono, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, EUSA, Ipsen Pharma, Janssen, Merck Serono, MSD, Pfizer, Telix; Financial Interests, Institutional, Coordinating PI: Bayer; Financial Interests, Personal and Institutional, Coordinating PI: Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Intuitive Surgical. K. Leucht: Financial Interests, Personal, Advisory Board, Detailed DOI on personal ESMO portal: see ESMO portal. F. Bozorgmehr: Financial Interests, Personal, Advisory Board: Amgen, Janssen, Novartis, AstraZeneca, Novocure, Daiichi Sankyo, BMS; Financial Interests, Personal, Invited Speaker: Novocure, AstraZeneca, MSD, Janssen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche, AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Janssen; Non-Financial Interests, Principal Investigator: AstraZeneca, GSK, Janssen, Amgen, Roche. P. Christopoulos: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda, Roche, Daiichi Sankyo; Financial Interests, Personal, Writing Engagement: Gilead; Financial Interests, Personal, Invited Speaker: Thermo Fisher; Financial Interests, Institutional, Funding: AstraZeneca, Boehringer Ingelheim, Amgen, Novartis, Roche; Financial Interests, Personal, Funding: Takeda. S. Rieken: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS; Financial Interests, Personal, Invited Speaker: Roche, Pfizer, Merck, Lilly, AstraZeneca, BMS; Financial Interests, Personal, Other, invited speaker and advisor: Aurikamed, onkowissen.de; Financial Interests, Institutional, Coordinating PI: Accuray, AstraZeneca; Non-Financial Interests, Member: DKG, POA, NOA; Non-Financial Interests, Leadership Role: ARO. J. Meran: Financial Interests, Personal, Advisory Board: Astellas, MSD, BMS; Financial Interests, Personal, Other, Conference Travel expenses: Roche, AstraZeneca, Amgen; Financial Interests, Personal, Speaker, Consultant, Advisor: PharmaMar, Janssen; Financial Interests, Institutional, Other, Study fees: Amgen, Panbela Therapeutics, Pierre Fabre, Astellas Pharma, Bayer, Bristol Myers Squibb Research, Gilead Science, AstraZeneca, Janssen, Merck Sharp Dohme, Morphosys, Celgene; Non-Financial Interests, Personal, Leadership Role: Arbeitsgruppe Ethik ÖGHO, Bioethik-Kommission Bundeskanzleramt Österreich. A. Stein: Financial Interests, Institutional, Advisory Board: BMS, MSD, Amgen, Merck, Daiichi Sankyo, Roche, GSK, Servier, Taiho; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Writing Engagement: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: BMS, MSD, Servier, German Cancer Aid, Pierre Fabre, Merck; Financial Interests, Institutional, Steering Committee Member: Novartis; Non-Financial Interests, Member: DGHO, ASCO. M. Binder: Financial Interests, Personal, Advisory Board: Mertelsmann Foundation, MSD, Roche; Financial Interests, Personal, Invited Speaker: MedMedia, Sachsen Anhaltische Krebsgesellschaft, Art Tempi; Financial Interests, Personal, Other, editor: Thieme; Financial Interests, Institutional, Funding: Novartis. N. Härtel: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Lilly, Daiichi, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Servier; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. K. Klinghammer: Financial Interests, Personal, Advisory Board: BMS, MSD; Financial Interests, Personal, Invited Speaker: Merck Sanofi, Onkowissen, Biontech; Non-Financial Interests, Principal Investigator: AstraZeneca, GSK, Kura Oncol., MSD, Biontech; Non-Financial Interests, Advisory Board: DGHO, DKG, AIO. V. Gruenwald: Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, BMS, Eisai, Ipsen, Janssen-Cilag, MSD, Merck Serono, Novartis, Pfizer, Gilead; Financial Interests, Personal, Advisory Board: Apogepha, BMS, Debiopharm, Eisai, MSD, Merck Serono, Oncorena, PCI Biotech, Pfizer, Roche, Cureteq, Synthekine; Financial Interests, Personal, Stocks/Shares: BMS, MSD, AstraZeneca, bicycle; Financial Interests, Institutional, Steering Committee Member: BMS, Novartis; Financial Interests, Institutional, Research Grant: Ipsen, MSD, Pfizer, BMS; Financial Interests, Personal and Institutional, Steering Committee Member: Eisai, Ipsen; Non-Financial Interests, Member: ASCO, German medical Oncology and Hematology Society; Non-Financial Interests, Advisory Role: German Cancer Society; Non-Financial Interests, Leadership Role: Working Group medical oncology; Other, Travel support to ESMO 2022: Pfizer; Other, Travel support for meeting: Merck Serono; Other, Travel Support ASCO GU 2024: Ipsen; Other, Travel Support: Janssen Cilag. M. Pogorzelski: Financial Interests, Personal, Advisory Board: Amgen, Merck Healthcare, MSD, BMS, Boehringer Ingelheim, GSK; Financial Interests, Personal, Invited Speaker: Amgen, Merck Healthcare, MSD, BMS, Boehringer Ingelheim, GSK; Financial Interests, Personal, Full or part-time Employment: University Hospital Essen, West German Cancer Center; Financial Interests, Institutional, Coordinating PI: MSD; Non-Financial Interests, Member: ESMO, DGHO, ASCO, EORTC; Non-Financial Interests, Leadership Role: AIO. All other authors have declared no conflicts of interest.