Impact of adherence to interstitial lung disease (ILD)/pneumonitis toxicity management guidelines (TMGs) on ILD/pneumonitis outcomes: A retrospective analysis of patients (pts) treated with trastuzumab deruxtecan (T-DXd) in DESTINY-Breast06 (DB-06).

1063 Background: DB-06 (NCT04494425) showed a progression-free survival benefit with T-DXd vs physician’s choice of chemotherapy for pts with hormone receptor–positive, HER2-low/-ultralow metastatic breast cancer, with no new safety signals. We report adherence rates to ILD/pneumonitis TMGs and their impact on ILD/pneumonitis outcomes. Methods: We retrospectively analyzed pts who received ≥1 dose of 5.4 mg/kg T-DXd and had adjudicated drug-related ILD/pneumonitis by the Mar 18, 2024 data cutoff. Adherence criteria were defined by ILD/pneumonitis severity at diagnosis (per investigator assessment) and associated TMGs (Table); adherence was classified as complete (CA), partial (PA), or non-adherence (NA) by TMG criteria met (all, ≥1 but not all, or none, respectively). Investigator-reported ILD/pneumonitis outcomes were ‘recovered’ (± sequelae), ‘recovering’, ‘not recovered’, and ‘fatal’. Results: Of 49 pts with adjudicated drug-related ILD/pneumonitis, respective rates of CA, PA, and NA were 73.5% (n=36), 14.3% (n=7), and 12.2% (n=6). By Mar 24, 2025, 66.7% (n=24) of pts with CA and 71.4% (n=5) with PA had an outcome of recovered ± sequelae, with no fatalities. Of pts with NA, 50% (n=3) did not recover, including one fatality. At diagnosis, 31 (63.3%), 15 (30.6%), and 3 (6.1%) pts had Grade (Gr) 1, 2, and 3 ILD/pneumonitis, respectively. Across all cases, 38.8% (n=19) progressed to a worse grade after diagnosis; progression from Gr 1 to Gr 2 represented 84.2% of progressions. Of 25 pts with Gr 1 ILD/pneumonitis and CA (optional steroid use), 16 received steroids and 9 did not; recovery rates were comparable (68.8% with steroids vs 66.7% without). For pts with Gr ≥2 ILD/pneumonitis and CA or PA (n=18), steroid use as recommended was associated with improved recovery rates (66.7% with steroids vs 33.3% without). Two pts with Gr 1 ILD/pneumonitis at diagnosis were rechallenged with 4.4 mg/kg T-DXd; both had recurrent Gr 1 ILD/pneumonitis but recovered. Conclusions: Adherence to ILD/pneumonitis TMGs was associated with improved ILD/pneumonitis outcomes in this small subset of pts. Steroid use as recommended for Gr ≥2 cases was associated with improved recovery. While further investigation of patient-level determinants of recovery is needed, these data demonstrate that adhering to ILD/pneumonitis TMGs may optimize ILD/pneumonitis outcomes. Clinical trial information: NCT04494425 . Adherence criteria by ILD/pneumonitis grade at diagnosis. Gr 1 Gr 2 Gr ≥3 T-DXd interrupted after AE onset Yes – – T-DXd discontinued after AE onset – Yes Yes 500–1000 mg/day methylprednisolone for 3 days – – Yes ≥1 mg/kg/day prednisone* – Yes Yes Steroid duration ≥14 days – Yes Yes ≥4-week taper – Yes Yes If no improvement 5 days from AE onset, switched to 2 mg/kg/day IV prednisone* – Yes Yes *Or equivalent; AE, adverse event.