Abstract PS1-01-15: A real-world experience of treatment rechallenge after grade 1 trastuzumab-deruxtecan related interstitial lung disease: clinical outcomes and blinded imaging review

Abstract Background: Trastuzumab-deruxtecan (T-DXd) is approved for advanced HER2+, low, and ultra-low advanced breast cancer, and multiple other solid tumors. T-DXd carries a rare but serious risk of ILD (incidence 12-15%), requiring frequent imaging and symptom evaluation. For > grade (G) 2 ILD, guidelines recommend permanent drug discontinuation. For asymptomatic G1 ILD, drug is held with the option for rechallenge (RC) after resolution of imaging findings. Limited data exist on T-DXd related ILD imaging findings and clinical outcomes after RC in patients (pts) treated in the real-world setting. Methods: We analyzed all pts treated with T-DXd at our institution from Sept 2018-June 2024. We identified pts with radiographic evidence of ILD by chart review. Adjudication of T-DXd related ILD was by treating provider and graded via CTCAE v5. A chest radiologist conducted a blinded review of baseline and follow-up chest CTs (up to 4 mos post T-DXd) for all pts treated with T-DXd, to identify possible cases of drug-related ILD and assess imaging improvement over time. Results: Of 214 pts treated with T-DXd, 44 (21%) developed ILD (27-G1, 8-G2, 4-G3, 3-G4, 2-G5). Median (med) ILD onset was 116 days (d) after 1st dose [range (r:) 9-833]. Among pts with ILD, 37 had breast, 5 had GI, 1 had lung, and 1 had head and neck cancer, with a med age of 59 yrs (r: 36-78), med 3 prior therapy lines for advanced disease (r: 0-13); 8/44 pts (18%) had renal impairment (CrCl