HER2-targeted agents and interstitial lung disease: A real-world pharmacovigilance analysis using FAERS data.

IntroductionThere has been a growing concern regarding the interstitial lung disease (ILD) associated with HER2-targeted agents. This study aimed to elucidate the risk and characteristics of ILD associated with anti-HER2 agents using the FDA Adverse Event Reporting System (FAERS).MethodsData from 2004 Q1 to 2024 Q2 were extracted from the FAERS. The significant association between HER2-targeted agents and ILD was evaluated using the reporting odds ratio (ROR). Risk factors for mortality and time-to-onset were also assessed.ResultsA total of 2262 cases of HER2-targeted agents-associated ILD were identified. Positive signals were detected in trastuzumab deruxtecan (T-Dxd) (ROR = 31.28, 95% confidence interval [CI] 29.22-33.48), trastuzumab emtansine (T-DM1) (ROR = 6.27, 95% CI 5.38-7.32), pertuzumab (ROR = 6.08, 95% CI 5.36-6.89), trastuzumab (ROR = 4.02, 95% CI 3.73-4.33), tucatinib (ROR = 1.84, 95% CI 1.25-2.71), and lapatinib (ROR = 1.37, 95% CI 1.12-1.68). However, only two cases of ILD were associated with neratinib. The overall median time-to-onset was 75.5 days (interquartile range: 27.0-163.0). Logistic regression analysis revealed that elderly patients, treatment with T-Dxd, and treatment for non-breast cancer were significant risk factors for fatal outcomes related to ILD associated with HER2-targeted agents.ConclusionThis study suggests a significant association between the ILD and HER2-targeted agents, including T-Dxd, T-DM1, pertuzumab, trastuzumab, tucatinib, and lapatinib.