PPIs effect in EGFR-TKI-associated interstitial lung diseases in patients with non-small cell lung cancer

Previous studies suggest a potential link between interstitial lung diseases (ILD) and EGFR-TKI use, with proton pump inhibitors (PPIs) possibly affecting EGFR-TKI-associated ILD differently. Our objective is to use the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to explore the potential link between ILD and the combination of PPIs and EGFR-TKI.

A retrospective examination of adverse event reports in the FAERS database spanning from the initial quarter of 2016 and the fourth quarter of 2023 was conducted. Disproportionality analysis, generalized linear models, and adjusted multivariable logistic regression were employed to assess the occurrence of EGFR-TKI-associated ILD in non-small cell lung cancer (NSCLC) patients receiving PPIs compared to those not receiving PPIs.

The reporting odds ratio (ROR) for PPIs combined with EGFR-TKIs demonstrated statistical significance (ROR 1.84, 95% CI 1.54-2.19). Significant increases were noted in both additive and multiplicative models (p < 0.001), as well as in the adjusted odds ratios derived from multivariate analysis (1.77, 95% CI 1.42-2.19, p < 0.001). Stratified analysis reveals that the combination of lansoprazole or esomeprazole and EGFR-TKI was linked to an elevated risk of ILD, with a ROR of 2.37 (95% CI 1.84-3.04) and 2.90 (95% CI 2.11-3.98), respectively, surpassing the risk associated with either medication used independently. Similarly, the ROR for osimertinib or gefitinib combined with PPIs stands at 2.20 (95% CI 1.83-2.66) and 2.33 (1.35-4.02), respectively, exceeding the risk when either drug is used alone.

Our study uncovered a heightened risk of ILD in NSCLC patients receiving certain EGFR-TKI in conjunction with specific PPIs, as opposed to EGFR-TKI monotherapy. Subsequent analysis indicates that different PPIs may elicit divergent effects on EGFR-TKI-associated ILD, with different EGFR-TKIs exhibiting distinct responses to combinations with different PPIs. Therefore, NSCLC patients undergoing such treatments should be meticulously monitored for ILD.