186P Exploratory pooled safety analysis of trastuzumab deruxtecan (T-DXd) in patients With HER2+ or HER2-low unresectable and/or metastatic breast cancer (mBC) in DESTINY-Breast trials

T-DXd is approved as 2L+ treatment for pts with HER2+ or HER2-low (IHC 1+/IHC 2+/ISH−) mBC based on efficacy in DESTINY-Breast (DB)-01/02/03/04 trials. There are no published pooled safety data for T-DXd in pts with mBC. Analysis included pts with HER2+ (DB-01/02/03) or HER2-low (DB-04) mBC. DB-01 was a single-arm study of T-DXd after trastuzumab emtansine (T-DM1). DB-02 compared T-DXd to treatment of physician's choice (TPC) after T-DM1. DB-03 compared T-DXd to T-DM1 after trastuzumab (± pertuzumab) + taxane. DB-04 compared T-DXd to TPC after 1 or 2 chemotherapy lines. Drug-related treatment-emergent adverse event (TEAE) rates for T-DXd were similar in DB-01/02/03/04 (Table). Median time (range) to T-DXd discontinuation due to any TEAE in DB-01/02/03/04 was 187.0 (8-783), 248.5 (2-759), 337.0 (104-1163), and 149.0 (3-740) d, respectively. Pooled T-DXd (N = 1216) adjudicated drug-related interstitial lung disease (ILD) rate was 12.7%; most grade 1 or 2 (11%); median (range) time to onset 176 (26-960) d; median (range) duration 56.5 (1-542) d. Rates of any-grade adjudicated drug-related ILD with T-DXd after <3/≥3 prior therapy lines were 14.3%/15.9% in DB-01, 7.1%/11.3% in DB-02, 17.9%/13.1% in DB-03, and 5.7%/13.2% in DB-04. Median treatment duration was ∼2-fold longer for pooled T-DXd (13.9 months; range, 0.2-45.1) vs comparators. Exposure-adjusted incidence rates of grade ≥3 TEAEs were 0.48 (T-DXd), 0.77 (TPC, DB-02), 0.65 (T-DM1), and 1.81 (TPC, DB-04) pt-years. Higher rates of drug-related nausea (72.4% vs 30.8%, 27.6%, 23.8%), vomiting (37.3% vs 11.8%, 5.7%, 9.9%), and fatigue (51.2% vs 31.3%, 29.1%, 42.4%) occurred with T-DXd vs TPC (DB-02), T-DM1 (DB-03), and TPC (DB-04).Table: 186PDrug-related TEAEs with T-DXd treatment, n (%)DB-01 N=184DB-02 N=404DB-03 N=257DB-04 N=371Reported in ≥40% of pts183 (99.5)394 (97.5)252 (98.1)357 (96.2)Nausea142 (77.2)277 (68.6)190 (73.9)271 (73.0)Fatigue110 (59.8)209 (51.7)123 (47.9)181 (48.8)Alopecia86 (46.7)142 (35.1)100 (38.9)141 (38.0)Vomiting81 (44.0)131 (32.4)115 (44.7)127 (34.2)Neutropenia63 (34.2)134 (33.2)115 (44.7)125 (33.7)Serious27 (14.7)46 (11.4)33 (12.8)49 (13.2)Associated with discontinuation33 (17.9)58 (14.4)51 (19.8)57 (15.4)Associated with dose reduction43 (23.4)95 (23.5)65 (25.3)83 (22.4)Associated with death3 (1.6)4 (1.0)07 (1.9) Open table in a new tab The safety profile of T-DXd was consistent in pts with HER2+ and HER2-low mBC across DB-01/02/03/04. Except in DB-03, ILD rates with T-DXd were similar or higher after ≥3 prior therapy lines.