376O Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Updated survival results of the randomized, phase III DESTINY-Breast04 study

DESTINY-Breast04 (NCT03734029) assessed T-DXd vs TPC in pts with HER2-low mBC (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization−). At primary data cutoff (DCO; January 11, 2022), median overall survival (mOS) for the full analysis set (FAS = hormone receptor-positive [HR+] and hormone receptor-negative [HR−]) was 23.4 months (mo) for T-DXd vs 16.8 mo for TPC (hazard ratio, 0.64; P = 0.001), with 18.4 mo median follow-up (F/U). Here, we report results from a pre-planned further F/U (DCO, March 1, 2023). Pts were randomly assigned 2:1 to T-DXd or TPC. At the updated DCO, analyses of OS (HR+ and FAS), progression-free survival (PFS) by investigator (HR+ and FAS), and safety were conducted. At DCO, median F/U was 32 mo. Median treatment duration was 8.2 mo (range, 0.2-39.1 mo) for T-DXd and 3.5 mo (range, 0.3-19.7 mo) for TPC. Efficacy results are shown in the table. Grade ≥3 treatment-emergent adverse events (TEAEs) were lower in T-DXd vs TPC (54.4% vs 67.4%). The most common TEAEs were gastrointestinal or hematological in nature; all-grade nausea (T-DXd: 76.0%; TPC: 30.2%) and vomiting (T-DXd: 40.7%; TPC: 13.4%) were most common for T-DXd and decreased neutrophil count (T-DXd: 22.1%; TPC: 36.0%) was most common for TPC. Exposure-adjusted incidence rates for any-grade TEAEs were 1.2 and 2.6 for the T-DXd vs TPC arm, respectively. No new adjudicated drug-related interstitial lung disease/pneumonitis events were reported with longer F/U (primary DCO: 45 pts [12.1%] for T-DXd; 1 pt [0.6%] for TPC). Results from the 32-mo median F/U for DESTINY-Breast04 confirms the sustained clinically meaningful improvement for T-DXd vs TPC previously demonstrated in HER2-low mBC, regardless of HR status. Similar to the primary analysis, the overall safety profile was generally manageable with longer duration of treatment exposure.Table: 376OSummary of efficacy resultsHR+FAST-DXd n = 331TPC n = 163T-DXdN = 373TPCN = 184mOS, mo (95% CI)23.9 (21.7-25.2)17.6 (15.1-20.2)22.9 (21.2-24.5)16.8 (14.1-19.5)mOS Hazard ratio (95% CI)0.69 (0.55-0.87)0.69 (0.55-0.86)OS rate at 24 mo, %a (95% CI)49.0 (43.3, 54.5)35.1 (27.3, 43.0)47.3 (41.9, 52.4)32.0 (24.8, 39.3)OS rate at 36 mo, %a (95% CI)26.5 (20.7-32.7)16.9 (10.2-25.0)26.2 (20.8-31.9)16.3 (10.3-23.6)mPFS by investigator, mo (95% CI)9.6 (8.4-10.0)4.2 (3.4-4.9)8.8 (8.3-9.8)4.2 (3.0-4.5)mPFS Hazard ratio (95% CI)0.37 (0.30-0.46)0.36 (0.29-0.45)m, median. Estimated and CI for OS rate at the specified time point are from Kaplan-Meier analysis. Open table in a new tab