Interstitial Lung Disease Incidence with Sequential Antibody–Drug Conjugate Use in MBC

Interstitial lung disease (ILD) is a known adverse event associated with antibody–drug conjugates (ADCs). However, the impact of sequential ADC treatments on ILD frequency in patients with metastatic breast cancer (MBC) is unknown. The current retrospective analysis was conducted to characterize the frequency and management of ILD with sequential use of ADCs in patients with MBC.

This multi-institution registry study identified patients with hormone receptor (HR)+/HER2-low and HR–/HER2-low MBC who had received both trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) monotherapy (in any order and with or without other intervening therapies) at 5 academic centers between 2020 and 2023.

A total of 84 eligible patients were included in this analysis. In this cohort of patients who received sequential ADC therapy, 14 patients developed ILD (all grades; 16.6%). The majority of these patients were White; median age was 64 years. Three patients had a prior smoking history, 9 had a prior cardiac or pulmonary comorbidity, and 9 patients had lung metastatic disease prior to receiving their first ADC.

All 14 patients were diagnosed with ILD during treatment with T-DXd; 7 patients subsequently received SG upon recovery from ILD with initial T-DXd treatment. The median time to ILD diagnosis was 3.8 months after initiation of T-DXd. The median time from initiation of T-DXd to first computed tomography scan was 7.9 weeks.

Half the ILD cases (n=7) were of grade 1/2 severity, and 4 were grade 3/4; 3 deaths were reported due to ILD. Seven of 14 patients had an increase in ILD grade. Overall, 12 of 14 patients were prescribed steroids for treatment; none received additional agents for ILD management. The time to recovery was 4.1 weeks. Two patients were re-challenged with T-DXd.

Based on these results, the authors concluded that there was no clear increased risk for ILD with sequential treatment of ADCs compared to historical controls and that practice patterns were consistent with recommended diagnostic evaluation and steroid management.

Source:

Mahtani R, Fisch S, Dempsey N, et al. Interstitial lung disease (ILD) in sequential antibody drug conjugate (ADC) use in patients with metastatic breast cancer (MBC): a multi-institutional experience. Presented at the 46th San Antonio Breast Cancer Symposium Annual Meeting, December 5-9, 2023; San Antonio, TX: Abstract PO4-12-06.