Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer
Top Cited Papers
- 30 March 2018
- journal article
- research article
- Published by Elsevier BV in Annals Of Oncology
- Vol. 29 (6), 1437-1444
- https://doi.org/10.1093/annonc/mdy103
Abstract
The composition of gut microbiota affects antitumor immune responses, preclinical and clinical outcome following immune checkpoint inhibitors (ICI) in cancer. Antibiotics (ATB) alter gut microbiota diversity and composition leading to dysbiosis, which may affect effectiveness of ICI. We examined patients with advanced renal cell carcinoma (RCC) and non-small-cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 mAb monotherapy or combination at two academic institutions. Those receiving ATB within 30 days of beginning ICI were compared with those who did not. Objective response, progression-free survival (PFS) determined by RECIST1.1 and overall survival (OS) were assessed. Sixteen of 121 (13%) RCC patients and 48 of 239 (20%) NSCLC patients received ATB. The most common ATB were β-lactam or quinolones for pneumonia or urinary tract infections. In RCC patients, ATB compared with no ATB was associated with increased risk of primary progressive disease (PD) (75% versus 22%, P < 0.01), shorter PFS [median 1.9 versus 7.4 months, hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.4–6.9, P < 0.01], and shorter OS (median 17.3 versus 30.6 months, HR 3.5, 95% CI 1.1–10.8, P = 0.03). In NSCLC patients, ATB was associated with similar rates of primary PD (52% versus 43%, P = 0.26) but decreased PFS (median 1.9 versus 3.8 months, HR 1.5, 95% CI 1.0–2.2, P = 0.03) and OS (median 7.9 versus 24.6 months, HR 4.4, 95% CI 2.6–7.7, P < 0.01). In multivariate analyses, the impact of ATB remained significant for PFS in RCC and for OS in NSCLC. ATB were associated with reduced clinical benefit from ICI in RCC and NSCLC. Modulatation of ATB-related dysbiosis and gut microbiota composition may be a strategy to improve clinical outcomes with ICI.Keywords
Funding Information
- Gustave Roussy Fondation Philanthropia
- RK Smiley Canadian Hematology Society
This publication has 33 references indexed in Scilit:
- Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II TrialJournal of Clinical Oncology, 2015
- Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: a prospective cohort studyBMC Infectious Diseases, 2014
- The Intestinal Microbiota Modulates the Anticancer Immune Effects of CyclophosphamideScience, 2013
- Commensal Bacteria Control Cancer Response to Therapy by Modulating the Tumor MicroenvironmentScience, 2013
- Tumour burden is an independent prognostic factor in metastatic renal cell carcinomaBJU International, 2012
- Diversity, stability and resilience of the human gut microbiotaNature, 2012
- Antibiotics, microbiota, and immune defenseTrends in Immunology, 2012
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal Of Cancer, 2009
- Long-term ecological impacts of antibiotic administration on the human intestinal microbiotaThe ISME Journal, 2007
- Escherichia coli Resistant to Fluoroquinolones in Patients with Cancer and NeutropeniaNew England Journal of Medicine, 1994