Comparative risk of interstitial lung disease (ILD) among Trastuzumab Deruxtecan (T-DXd) and other anti-breast cancer drugs: a VigiBase pharmacovigilance study approach.

<bold>Background:</bold> Chemotherapies are among the main providers of ILD. The aim of this study is to compare T-DXd and other anti-breast cancer drugs associated ILD reports. <bold>Methods:</bold> We performed a disproportionality analysis of ILD with anti-breast cancer drugs using VigiBase, the WHO pharmacovigilance database, until 02/06/2024, using the information component (IC). An IC0.25>0 was considered statistically significant. Main characteristics of T-DXd-ILD reports were analysed. <bold>Results:</bold> With an IC0.25 of 6.6, T-DXd is the drug the most associated with ILD compared with other anti-breast cancer drugs (p<0.001) for which the IC0.25 does not exceed 3.6. As a comparison, trastuzumab alone, trastuzumab emtansine and pertuzumab have respectively an IC0.25 of 3.0, 3.3 and 3.6. A total of 714 reports of T-DXd-ILD are registered in VigiBase, with a sex ratio of 18 women/men and a mean age of 59 years old. Over 77.3% of the reports are serious with a mortality of 19%. On average, the time to onset is 150 days and T-DXd is the only suspect drug in 97% of cases. Issues from 66 out of 266 rechallenges after T-DXd withdrawn and ILD improvement were informative. ILD recurrence was observed in 10 (15%) rechallenges but not in the 56 (85%) others. The lack of information on other risk factors for ILD including previous therapeutic lines and radiotherapy is a limitless of our study. <bold>Conclusion:</bold> VigiBase showed that T-DXd is the mostly drug associated with ILD occurrence compared to other anti-breast cancer drugs. It reported a high frequency of seriousness and mortality. Early detection and case-by-case analysis of T-DXd-ILD are paramount.