Equivocal and definite interstitial lung abnormalities as risk factors for trastuzumab deruxtecan-related interstitial lung disease in breast cancer

Abstract

Abstract Background Trastuzumab deruxtecan (T-DXd) is effective for advanced breast cancer but is associated with interstitial lung disease (ILD). The clinical relevance of baseline interstitial lung abnormalities (ILAs), including subtle equivocal findings, remains unclear. Methods This retrospective cohort study included consecutive patients with advanced or recurrent breast cancer who initiated T-DXd at a tertiary hospital in Japan between June 2020 and May 2025. Baseline CT before T-DXd initiation was reviewed for ILAs and classified as no ILA, equivocal ILA, or definite ILA. The cumulative incidence of T-DXd-related ILD was estimated using a competing-risk approach. Results Among 156 patients, baseline ILAs were identified in 50 patients: 21 with equivocal ILA and 29 with definite ILA. T-DXd-related ILD occurred in 31 patients (20%), including 19 of 50 patients (38%) in the ILA group and 12 of 106 patients (11%) in the non-ILA group. Baseline ILA was associated with a higher cumulative incidence of T-DXd-related ILD (subdistribution hazard ratio, 3.56; 95% CI, 1.63-7.78; P = .001). No significant difference in T-DXd-related ILD risk was detected between the equivocal and definite ILA groups. This association remained consistent in the <1.5-mm CT subgroup. No significant differences in progression-free or overall survival were observed according to baseline ILA status. Among patients with baseline ILA, 33 of 50 had ILAs first detected during prior systemic anticancer therapy. Conclusions Baseline ILAs, including equivocal findings, were associated with an increased risk of T-DXd-related ILD. ILAs were frequently first detected during prior systemic anticancer therapy before T-DXd initiation.