Global Disproportionality Analysis of Adverse Event Reports on Interstitial Lung Diseases for Cancer-Targeted Therapies, 1968-2024.

[BACKGROUND AND OBJECTIVES] The increasing complexity of interstitial lung disease (ILD) related to cancer-targeted monoclonal antibodies (mAbs) has emerged as a significant clinical concern. Thus, this study aimed to investigate reporting signals of four ILD subtypes detected with cancer-targeted mAbs.

[METHODS] This global pharmacovigilance study conducted disproportionality analyses to detect signals of ILD subtypes reported with cancer-targeted mAbs. ILD subtypes were classified into eight categories according to previous studies, of which four with a low number of reports were excluded. Five cancer-targeted monoclonal antibodies (VEGF/VEGFR, CD20, PD-1/PD-L1, HER2, and EGFR inhibitors) were included according to ATC code (L01F). Reporting signals were evaluated using reporting odds ratio (ROR) with 95% CI and information component (IC) with IC.

[RESULTS] Interstitial pneumonitis and pulmonary fibrosis showed significant disproportionate reporting signals across all drugs. Notably, interstitial pneumonitis showed significant signals with EGFR inhibitors (ROR, 47.46 [95% CI, 44.67-50.42]; IC, 5.47 [IC, 5.37]) and PD-1/PD-L1 inhibitors (45.20 [43.49-46.97]; 5.36 [5.30]), while pulmonary fibrosis showed higher signals with CD20 inhibitors (12.71 [11.30-14.31]; 3.61 [3.42]). Organising pneumonia exhibited significant signals with PD-1/PD-L1 inhibitors (ROR, 44.48 [95% CI, 39.05-50.67]; IC, 5.26 [IC, 5.04]), followed by CD20 (17.45 [13.88-21.94]; 3.95 [3.57]), and HER2 (15.95 [11.88-21.40]; 3.76 [3.26]), with the strongest signal observed with PD-1/PD-L1 inhibitors. Eosinophilic pneumonia showed significant signals with all drugs except CD20 inhibitors.

[CONCLUSIONS] Although causal inference cannot be drawn, this global disproportionality study highlights reporting signals between cancer-targeted mAbs and ILD subtypes, underscoring the importance of strengthening adverse event reporting systems before and after mAb administration.