TOPLINE:

In a cohort study of patients with advanced non-small cell lung cancer (NSCLC), exposure to certain antibiotics, high-dose steroids, or proton pump inhibitors (PPIs) at the start of immunotherapy was associated with poorer overall survival.

METHODOLOGY:

• Immune checkpoint inhibitors have significantly improved outcomes for patients with NSCLC. However, many patients are prescribed antibiotics, steroids, or PPIs during immunotherapy — which is suspected of potentially interfering with treatment by altering gut microbiota or suppressing the immune system. Studies looking at those co-medications and patients’ outcomes have reported inconsistent results.
• This retrospective study used the French national healthcare database to identify 41,529 patients newly diagnosed with NSCLC (median age, 65 years; 67% men) from 2015 to 2022. All patients received first-line pembrolizumab and survived at least 2 months after treatment initiation: 35.7% received pembrolizumab alone, and 64.3% received pembrolizumab plus chemotherapy.
• Exposure to antibiotics and PPIs was defined as two or more prescriptions from 60 days before to 42 days after the initiation of pembrolizumab; exposure to steroids was defined as two or more prescriptions from 30 days before to 30 days after immunotherapy initiation. At the start of treatment, 41.9% of patients were exposed to antibiotics, 59.1% to steroids, and 53.7% to PPIs.
• The primary outcome was overall survival. Inverse probability of treatment weighting was used to adjust for comorbidities, other medications, and additional confounders.

TAKEAWAY:

• After adjustment, antibiotic use was associated with worse overall survival (hazard ratio [HR], 1.08; P < .001). The exceptions were macrolides and penicillin, which were not associated with survival among patients receiving either pembrolizumab alone or combination therapy.
• Certain antibiotics were associated with stronger effects on overall survival — including fluoroquinolones (HR, 1.22; P = .004) and sulfonamides (HR, 1.56; P < .001) among patients who received combination therapy, and beta lactams other than penicillin among patients who received pembrolizumab alone (HR, 1.28; P = .02).
• Exposure to PPIs was associated with worse overall survival (HR, 1.13; P < .001) regardless of treatment regimen, particularly lansoprazole (HR, 1.17; P < .001), pantoprazole (HR, 1.17; P < .001), and multiple PPI prescriptions (HR, 1.33; P < .001).
• Steroid use was associated with worse overall survival among patients on pembrolizumab alone (HR, 1.17; P < .001), particularly at doses > 20 mg/d (P for trend = .005). Among patients who received combination therapy, steroid use was tied to improved survival (HR, 0.88; P < .001), but doses > 30 mg/d were associated with worse survival (P for trend < .001).

IN PRACTICE:

The findings suggest that for patients beginning immunotherapy, co-medications “should be monitored carefully,” the authors wrote. More specifically, they suggested that antibiotic choice could be “oriented toward” macrolides or penicillin, while PPIs should be avoided except when necessary for indications such as gastric ulcer.

SOURCE:

This study, led by Adrien Rousseau, MD, Thoracic Group and International Center for Thoracic Cancers, Paris-Saclay University, Villejuif, France, was published online in JAMA Network Open.

LIMITATIONS:

This study lacked data on hospital medication use and brain metastases. Additionally, the indications for various exposures were unknown, while residual confounding could be present despite adjustment.

DISCLOSURES:

The authors did not disclose any funding information. Several authors reported receiving personal fees or having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.