704P - Regional differences in drug-induced lung disease (DILD) caused by anticancer drugs between the US, EU and Japan: A large-scale data-based analysis using the FDA Adverse Event Reporting System (FAERS)

Background

DILD is a significant adverse event with a high fatality rate, and risk factors related to DILD have not been determined. Previous reports indicated regional differences in DILD. However, no large-scale data-based analyses investigating regional differences in DILD have been reported.

Methods

Adverse events report from the FAERS between January 2010 and December 2020 were collected. Regional differences in DILD incidence were examined based on data from the United States (US), Europe (EU), and Japan (JP). Multivariable logistic regression analysis, including the type of agent (tyrosine kinase inhibitors: TKIs, immune checkpoint inhibitors: ICIs, antibody-drug conjugate: ADCs, and cytotoxic agents) as confounding factors, was performed to calculate the reporting odds ratios (RORs).

Results

We identified reports of DILD from the US, EU and JP (74548, 31009, and 23004). Results of univariate analysis showed significantly higher RORs of anticancer drugs for reports from JP and EU compared to those from the US (JP, ROR 4.432 [95% CI, 4.366-4.499], p<0.001; EU, ROR 1.291 [95%CI, 1.274-1.308], p<0.001). Results of multivariable analysis for each single agent regimen of anticancer drugs showed that, for all regimens, reports from JP had significantly higher RORs compared to those from the US (TKIs, ROR 3.274 [95%CI, 3.105-3.451], p<0.001; ICIs, ROR 2.170 [95%CI, 2.025-2.325], p<0.001; ADCs, ROR 2.335 [95%CI, 1.666-3.272], p<0.001; cytotoxic agents, ROR 3.989 [95%CI, 3.776-4.215], p<0.001). Reports from the EU showed higher RORs for TKIs and cytotoxic agents than the US, but no significant difference between ICIs and ADCs (TKIs, ROR 1.679 [95%CI, 1.594-1.769], p=0.0034; ICIs, ROR 1.041 [95%CI, 0.965-1.123], p=0.2960; ADCs, ROR 1.046 [95%CI, 0.763-1.434], p=0.7804; cytotoxic agents, ROR 1.418 [95%CI, 1.354-1.485], p<0.001).

Conclusions

Reports from JP had significantly higher RORs than those from the US for all anticancer drug regimens. Further, reports from the EU had higher RORs than the US for TKIs and cytotoxic agents, but no significant difference among ICIs and ADCs. Japanese patients may have a higher risk for DILD than US and EU patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.