A new study suggests that antibiotics may reduce the efficacy of immune checkpoint inhibitors (ICIs) in older patients with cancer, but this depends on the type of cancer, antibiotic, and ICI in question.
The study showed that exposure to fluoroquinolones before starting ICI therapy was associated with worse overall survival (OS), but there was no such association for penicillin or cephalosporin exposure.
Fluoroquinolone exposure was associated with worse OS in patients treated with nivolumab or pembrolizumab but not in those who received ipilimumab. And fluoroquinolone exposure was associated with worse OS in patients with lung cancer or melanoma but not those with renal cancer.
These findings were published in the Journal of Clinical Oncology.
This retrospective study included 2737 cancer patients (age 65 and older) who began treatment with ICIs between June 2012 and October 2018. The median age of the cohort was 73 years. Patients had lung cancer (53%), melanoma (34%), renal cancer (7%), bladder cancer (3%), head and neck cancer (2%), and other cancers (2%).
The most commonly used ICIs were nivolumab alone (43%), pembrolizumab alone (41%), and ipilimumab alone (13%). Most patients (59%) were exposed to antibiotics in the year before starting ICI therapy, and 19% were exposed within 60 days before ICI initiation. Antibiotic exposure was defined as filling at least 1 prescription within the designated time period.
Results by Type of Antibiotic and ICI
In a multivariate analysis, antibiotic exposure up to 1 year before starting ICI therapy was significantly associated with worse OS (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.01-1.24; P =.03).
This result appeared to be driven by an association between worse OS and fluoroquinolone exposure within 1 year prior to starting ICI therapy (aHR, 1.26; 95% CI, 1.13-1.40; P <.001). There was no association between penicillin or cephalosporin exposure and OS.
The association between worse OS and fluoroquinolone exposure up to 1 year before ICI treatment was present for patients treated with nivolumab or pembrolizumab (aHR, 1.28; 95% CI, 1.15-1.44; P <.001) but not ipilimumab (aHR, 1.00; 95% CI, 0.70-1.44; P =.98).
Results by Cancer Type
When the researchers looked at outcomes by cancer type, they found no association between OS and antibiotic exposure within 1 year or 60 days in lung cancer, melanoma, or renal cancer. Likewise, there were no associations between OS and penicillin or cephalosporin exposure across cancer types.
There was an association between worse OS and fluoroquinolone exposure up to 1 year before ICI treatment for patients with lung cancer (aHR, 1.22; 95% CI, 1.06-1.39; P =.005) but not for those with melanoma or renal cancer.
There was also an association between worse OS and fluoroquinolone exposure within 60 days before ICI treatment for patients with melanoma (aHR, 1.66; 95% CI, 1.12-2.47; P =.01) but not for those with lung cancer or renal cancer.
“In this population-level study, exposure to antibiotics and specifically fluoroquinolones before ICI therapy was observed to be associated with worse OS among older adults with cancer,” the researchers concluded. “Interventions aimed at altering the gut microbiome to boost immunogenicity may help improve outcomes for patients receiving ICIs with prior antibiotic exposure.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Eng L, Sutradhar R, Niu Y, et al. Impact of antibiotic exposure before immune checkpoint inhibitor treatment on overall survival in older adults with cancer: A population-based study. J Clin Oncol. Published online February 24, 2023. doi:10.1200/JCO.22.00074