Temporal Trends in Antineoplastic Agent-associated Interstitial Lung Disease Involving Immune Checkpoint Inhibitors in the JADER Database

In Vivo. 2026 Jul-Aug;40(4):2264-2273. doi: 10.21873/invivo.14378.

ABSTRACT

BACKGROUND/AIM: Cancer pharmacotherapy has advanced substantially with the introduction of novel agents such as immune checkpoint inhibitors (ICIs). However, managing drug-induced interstitial lung disease (DIILD) associated with these agents remains a major clinical challenge in maintaining treatment. Detailed investigations into recent changes in DIILD reporting and specific drug categories contributing to these changes remain limited. Therefore, we aimed to identify factors contributing to recent changes in DIILD reports by analyzing temporal trends in antineoplastic agent-associated DIILD using the Japanese Adverse Drug Event Report database.

MATERIALS AND METHODS: We analyzed the database reports from 2004 to 2024. The reporting odds ratio (ROR) and Weibull model were used to evaluate safety signals and the time to onset of ICI-associated DIILD, respectively.

RESULTS: The mean rate of antineoplastic agent-associated DIILD among total adverse event reports was significantly higher in the most recent period (2016-2024) than in the earlier period (2004-2015) (25.9% vs. 15.3%, p<0.05). An analysis by drug category suggested that an increase in ICI-associated reports from 2016 onward largely contributed to this upward trend. Significant signals were detected for ICI-associated DIILD (ROR for total reports: 4.13; ROR for reports with fatal outcomes: 2.73). Furthermore, there has been a shift towards combination therapy with ICIs and cytotoxic chemotherapy, accounting for the largest proportion of reports with fatal outcomes of ICI-associated DIILD in 2024. The Weibull analysis indicated an early failure pattern for ICI-associated DIILD.

CONCLUSION: The recent increase in antineoplastic agent-associated DIILD may primarily be driven by the expanding use of ICIs, particularly ICI in combination with chemotherapy. Because DIILD tends to occur in the early phase of treatment, strict monitoring is warranted during the initial therapy period.

PMID:42379756 | PMC:PMC13322017 | DOI:10.21873/invivo.14378