ATLANTA – The use of antibiotic therapy appears to adversely affect the efficacy of immune checkpoint inhibitors in non-small cell lung cancer patients.
That’s according to a study at the 2021 American Society of Clinical Oncology (ASCO) annual meeting.1
Researchers from the Atlanta VA Healthcare System and Emory University School of Medicine pointed out that dysregulation of the gut microbiota caused by antibiotic therapy (Abx) can alter the anticancer immune response. They cited several small studies which have associated antibiotic use with reduced ICI efficacy in NSCLC patients.
The study team sought to confirm that with a trial in a larger population of NSCLC patients treated with the cutting-edge therapy. To do that, researchers conducted a nested cohort study of veterans who were diagnosed with NSCLC between 2010 and 2018 and treated with ICI.
As part of the VHA study, two exposures to antibiotics were specified and separately analyzed: prior Abx (pAbx) was defined as receipt of an Abx prescription within 30 days prior to initiation of ICI, and concurrent Abx (cAbx) was defined as receipt of an Abx prescription within 60 days following ICI initiation.
Participants included 3,634 veterans who received ICI, with most of them treated with nivolumab (59.3%) or pembrolizumab (35.1%). With a median age of 69, most, 97%, were male and white, 73%. The majority, 60.4%, had one or more co-morbidities, 47.8% had adenocarcinoma and 40.9% had stage IV disease at diagnosis. Of the 21% of veterans prescribed pAbx, the most common classes were beta-lactams, quinolones, and macrolides.
Results indicated that those patients, with prior antibiotic use, had shorter overall survival than those without pAbx — median seven vs. 10 months. In the propensity-matched cohort analysis, veterans receiving pAbx had lower OS (HR 1.27, p<0.01) For the cAbx analysis, 3,223 veterans survived to the two-month landmark, with 30.1% of those receiving cAbx. Still, those veterans had shorter OS than those without cAbx — median 7 vs. 10 months.
“In the largest analysis to date of Abx use in NSCLC patients receiving ICI, receipt of Abx within either 30 days before or 60 days after start of ICI was associated with lower OS,” researchers concluded. “These findings suggest Abx therapy may have a detrimental effect on immunotherapy outcomes.”
- Stokes WA, Behera M, Jiang R, Gutman D. (June 4-8, 2021) Effect of antibiotic therapy on immunotherapy outcomes for non-small cell lung cancer: Analysis from the Veterans Health Administration Database. ASCO 2021 annual meeting. Virtual. https://meetinglibrary.asco.org/record/198518/abstract
