185O Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): A detailed safety analysis of the randomized, phase III DESTINY-Breast04 trial

Abstract

DESTINY-Breast04 (NCT03734029) demonstrated significantly improved overall and progression-free survival (PFS) with T-DXd vs TPC in pts with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization-negative) mBC, with manageable safety. Here, we report additional safety data. Pts with centrally confirmed HER2-low mBC, treated with 1-2 prior lines of chemotherapy, were randomly assigned 2:1 to receive T-DXd or TPC. An analysis of selected treatment-emergent adverse events (TEAEs) and age (<65 vs ≥65 years [y]) was done; endpoints included time to first onset (TTO), duration of first event (DUR), and resolution. At data cutoff (January 11, 2022), median (m) treatment duration was 8.2 months (mo; range [r], 0.2-33.3) for T-DXd vs 3.5 mo (r, 0.3-17.6) for TPC. Exposure-adjusted incidence rates (EAIRs; per pt-y) for any-grade TEAEs were lower for T-DXd vs TPC (1.30 vs 2.66). mTTO and mDUR of any-grade interstitial lung disease (ILD) in pts treated with T-DXd were 129 days (d; r, 26-710 d) and 47 d (r, 13-365 d). 13 pts had adjudicated drug-related grade 1 ILD; of those pts, 6 were rechallenged with T-DXd after resolution (details to be presented). Incidence of any-grade drug-related neutropenia (NP) and febrile NP was lower for T-DXd vs TPC; subsequent granulocyte colony-stimulating factor use was 6.7% vs 19.8%. Nausea/vomiting (N/V) events in T-DXd vs TPC were 79.5% vs 35.5%. T-DXd-treated pts received more antiemetic prophylaxis (AP; 50.9%) vs TPC-treated pts (37.2%); 92.3% of T-DXd and 68.8% of TPC N/V events in AP-treated pts resolved. Incidence of any-grade drug-related TEAE was consistent between pts aged <65 y and ≥65 y. For T-DXd, incidence of grade ≥3 TEAEs and TEAEs associated with drug discontinuations (DD) was higher in pts aged ≥65 y compared to those aged <65 y; the most common TEAE associated with DD was ILD/pneumonitis. However, mPFS favored T-DXd over TPC in all patients, regardless of age. EAIR, TTO, and DUR data for selected TEAEs will be presented. T-DXd demonstrated a manageable safety profile to support its use as the new standard of care in pts with HER2-low mBC.