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

Year: 2025

Type: article

Abstract: ABSTRACT 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 025 . 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 0.25 , 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 0.25 , 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.

Source: Respirology

DOI: 10.1002/resp.70135