An age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03.

1006 Background: T-DXd is approved for use in pts with HER2+ unresectable or mBC after a prior anti-HER2-based regimen in the metastatic or (neo)adjuvant setting, based on the randomized phase 3 DESTINY-Breast03 study (Cortes et al. N Engl J Med 2022). Older pts with HER2+ mBC tend to have worse efficacy and safety outcomes, regardless of treatment (Evans et al. Cancer Res 2021). Outcomes of older pts treated with T-DXd have not been thoroughly examined. Here we report age-specific (<65 vs ≥65 years) efficacy and pooled safety analyses of T-DXd from DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03. Methods: DESTINY-Breast01 (data cutoff [DCO], March 26, 2021) and DESTINY-Breast02 (DCO, June 30, 2022) enrolled pts whose disease progressed on trastuzumab emtansine (T-DM1); DESTINY-Breast02 compared T-DXd to chemotherapy of physician’s choice. DESTINY-Breast03 (DCO, July 25, 2022) included pts previously treated with trastuzumab and taxane; pts received either T-DXd or T-DM1. Results: At baseline, there were 44 (23.9%), 85 (20.9%), and 49 (18.8%) pts ≥65 years of age who received T-DXd in DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03, respectively. At DCO, median pooled treatment duration with T-DXd was 13.1 mo (range, 0.7-44.0) for pts <65 and 12.4 mo (range, 0.7-45.1) for pts ≥65. Key efficacy data are shown in the Table. Any-grade treatment-emergent adverse events (TEAEs), grade ≥3 TEAEs, and serious AEs were observed in 99.6%, 53.6%, and 24.3% of pts <65 and 100%, 65.5%, and 32.2% of pts ≥65, respectively. There were 125 (18.7%) and 45 (25.4%) TEAEs associated with T-DXd discontinuation in pts aged <65 and ≥65, respectively. Any-grade adjudicated drug-related interstitial lung disease/pneumonitis occurred in 11.8% of pts <65 and 17.5% of pts ≥65; grade 5 events occurred in 0.9% and 0.6% of pts <65 and ≥65, respectively. Additional efficacy and safety data will be presented. Conclusions: Results from this pooled analysis further demonstrate that T-DXd has a favorable benefit-risk profile in pts ≥65 years, with slightly increased toxicity, as expected. Clinical trial information: NCT03248492 , NCT03523585 , NCT03529110 . [Table: see text]