In a study reported in the Journal of Clinical Oncology, Eng et al found that exposure to antibiotics within 1 year of starting immune checkpoint inhibitor therapy was associated with poorer survival among patients with cancer who were aged 65 years and older.
Study Details
The population-based retrospective cohort study included patients with cancer aged ≥ 65 years who initiated treatment with immune checkpoint inhibitors between June 2012 and October 2018 in Ontario, Canada. The cohort was linked to health-care databases to identify antibiotic prescription claims data at 1 year and 60 days before the start of immune checkpoint inhibitor therapy.
Key Findings
Among the 2,737 patients included in the analysis, the median age was 73 years; the most common cancers were lung (in 53% of patients), melanoma (34%), and genitourinary (7% renal, 3% bladder); and the first immune checkpoint inhibitors received were nivolumab in 43% and pembrolizumab in 41%.
KEY POINTS
- Antibiotic exposure within 1 year of starting immune checkpoint inhibitors was associated with worse overall survival; receipt of antibiotics within 60 days was not associated with significantly poorer survival.
- No significant association of survival with exposure to penicillins or cephalosporins was observed.
- Use of fluoroquinolones was associated with significantly poorer survival across multiple time points.
Overall, 59% of patients received antibiotics within 1 year and 19% within 60 days of starting immune checkpoint inhibitors. Median overall survival was 306 days in the entire cohort. On multivariate analysis, antibiotic exposure within 1 year of starting immune checkpoint inhibitors was associated with worse overall survival (adjusted hazard ratio [aHR] = 1.12, 95% confidence interval [CI] = 1.12–1.23, P = .03). Receipt of antibiotics within 60 days was not associated with significantly poorer survival (aHR = 1.06, 95% CI = 0.94–1.20, P = .35). No significant associations with survival were observed for total weeks or total doses of antibiotic treatment within 1 year or 60 days.
In analysis by antibiotic class, no significant association of survival with exposure to penicillins or cephalosporins was observed. The use of fluoroquinolones within 1 year was associated with significantly poorer survival (aHR = 1.26, 95% CI = 1.13–1.40, P < .001) and use within 60 days was associated with numerically poorer survival (aHR = 1.20, 95% CI = 0.99–1.45, P = .06); total weeks of exposure over 1 year (aHR = 1.07 per week, 95% CI = 1.03–1.11, P < .001) and within 60 days (aHR = 1.12 per week, 95% CI = 1.03–1.23, P = .01) were associated with poorer survival.
The investigators concluded, “In this population-level study, exposure to antibiotics and specifically fluoroquinolones before immune checkpoint inhibitor therapy was observed to be associated with worse overall survival among older adults with cancer. Interventions aimed at altering the gut microbiome to boost immunogenicity may help improve outcomes for patients receiving immune checkpoint inhibitors with prior antibiotic exposure.”
Lawson Eng, MD, SM, of the Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Ministry of Long-Term Care, the ASCO/Conquer Cancer Foundation—Young Investigator Award, and others. For full disclosures of the study authors, visit ascopubs.org.
