Atlanta, GA—The use of antibiotic therapy appears to adversely affect the efficacy of immune checkpoint inhibitors (ICI) in non-small cell lung cancer patients.
That’s according to a study at the 2021 American Society of Clinical Oncology (ASCO) annual meeting.
Researchers from Emory University School of Medicine and colleagues pointed out that dysregulation of the gut microbiota caused by antibiotic therapy (Abx) can alter the anticancer immune response. They cite several small studies that 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 ICI within the Veterans’ Health Administration. 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 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 comorbidity or more, 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 (OS) than those without pAbx—median 7 months versus 10 months. In the propensity-matched cohort analysis, veterans receiving pAbx had lower OS (HR 1.27; P <.01). For the cAbx analysis, 3,223 veterans survived to the 2-month landmark, with 30.1% of those receiving cAbx. Still, those veterans had shorter OS than those without cAbx —median 7 months versus 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,” the researchers concluded. “These findings suggest Abx therapy may have a detrimental effect on immunotherapy outcomes.”
Other studies released at the ASCO meeting discussed two drug classes that showed promise for enhancing the effect of ICIs.
In one study, some of the same researchers discussed the benefits of concomitant nonsteroidal anti-inflammatory (NSAID) medications with immunotherapy. With a median follow-up of 8 months, their results indicated that exposure to concomitant NSAIDs was associated with longer OS (HR = 0.90; 0.83-0.98; P = .01) after adjusting for all available potential confounders on multivariable analyses. The researchers explained that longer OS persisted following propensity score matching (HR = 0.89; 0.82-0.97; P = .007).
The study team also looked at certain azole derivatives as having antitumor efficacy and the benefit of modulated responses to ICIs, explaining, “Clinical evidence of synergy can support ongoing research that is investigating the role of repurposing current FDA-approved azole medications to improve outcomes in people with non-small cell lung cancer (NSCLC).”
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