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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Tuesday, October 7, 2025
A recent nationwide French cohort study found that certain comedications may be a detriment to immunotherapy efficacy in advanced non–small-cell lung cancer (NSCLC) and may be associated with worse overall survival (OS) outcomes. The study, published in JAMA Network Open, evaluated the effects of concomitant antibiotic, corticosteroid, or proton pump inhibitor (PPI) use with first-line pembrolizumab, alone or in combination with chemotherapy.
The cohort study was made up of 41,529 patients with advanced NSCLC starting first-line pembrolizumab therapy, identified in the French National Health Data System between 2015 and 2022. Comedication exposure was defined around the immunotherapy start window: for antibiotics and PPIs, at least 2 prescriptions from 60 days before to 42 days after, and for steroids at least 2 prescriptions 30 days before to 30 days after. Propensity score–weighted Cox models and weighted Kaplan-Meier methods estimated hazard ratios (HRs) and 24-month absolute survival differences.
Excluding macrolides and penicillins, antibiotics were associated with worse OS with pembrolizumab + chemotherapy (HR 1.12; absolute difference –3.65%). After adjusting for interaction, antibiotic exposure was not significantly associated with OS (HR 1.02; 95% CI 0.97 to 1.08) in the pembrolizumab alone population. (Note: Specific types of antibiotics were associated with worse OS in this group.) PPI use was independently associated with worse OS, with no significant difference by regimen (HR 1.13, 95% CI 1.10–1.17; absolute 24-month decrement –4.4%). Overall, steroid exposure was not statistically associated with OS in the pooled cohort (HR 0.98, 95% CI 0.95–1.02), however interactions by treatment regimen emerged. In patients receiving pembrolizumab monotherapy, use of steroids > 20 mg prednisone equivalent correlated with worse survival, while in those receiving chemoimmunotherapy low to moderate steroid dosing (10–20 mg) was linked to improved OS.
The authors concluded that certain concomitant comedications may exert detrimental effects on immunotherapy efficacy and cautioned oncologists to carefully consider the use of antibiotics, steroids, and PPIs when initiating pembrolizumab in NSCLC.
Disclosures: For full disclosures of study authors, visit jamanetwork.com.
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