Antineoplastic agent-associated interstitial lung disease in breast, ovarian, and prostate cancers: a pharmacovigilance study using the FDA adverse event reporting system

Interstitial lung disease (ILD) is a potentially fatal adverse effect of anticancer therapy, but comparative ILD reporting associations across antineoplastic agents in sex hormone-sensitive solid tumors (breast, ovarian, and prostate cancers) remain unclear. This study aimed to compare ILD reporting associations among antineoplastic agents used in these malignancies and to provide external clinical context from the published literature. We analyzed FAERS reports of ILD associated with 65 prespecified antineoplastic agents used in patients with sex hormone-sensitive solid tumors. Each drug’s ILD reporting association was evaluated using disproportionality analysis (reporting odds ratios), multivariable regression, and time-to-onset analyses. In addition, we conducted a structured PubMed search through March 15, 2026 for eligible human case reports and case series involving these agents. Among 8, 146 FAERS ILD reports, trastuzumab deruxtecan (T-DXd) showed a prominent ILD signal and the highest adjusted reporting association. Some sex hormone-pathway agents, including darolutamide and fulvestrant, also showed elevated ILD reporting associations, and concomitant SHA analyses identified additional signals. Older age and lower body weight were independently associated with ILD reporting. In exploratory complete-case TTO analyses, death-recorded ILD reports showed a shorter median reported TTO than non–death-recorded ILD reports; in FDR-adjusted body-weight–stratified analyses, this pattern was observed in the ≥70 kg subgroup but not in the <70 kg subgroup and should be interpreted as hypothesis-generating. The literature review identified 85 eligible publications comprising 98 case-level records and provided supportive clinical context for the FAERS findings. Overall, ILD reporting associations vary across antineoplastic agents used for sex hormone-sensitive solid tumors, even within the same class. Notably, underemphasized signals were observed for certain SHAs. These findings support early ILD monitoring and attention to patient factors such as age and body weight, while underscoring the need for cautious interpretation and confirmation in prospective and real-world studies.