192MO DESTINY-Breast04 subgroup analyses of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with human epidermal growth factor 2 (HER2)-low, estrogen-receptor (ER) expression immunohistochemistry (IHC) 0-10% metastatic breast cancer (mBC)

In the phase III DESTINY-Breast04 trial (NCT03734029), T-DXd significantly improved progression-free survival (PFS) and overall (OS) vs TPC in pts with HER2-low mBC regardless of hormone receptor expression. Breast cancers low ER expression (IHC 1-10%) represent a subset that may mimic clinical behavior triple-negative breast cancer. Here, we report analyses IHC 0% 1-10%. Pts (HER2 1+ or 2+/ISH−) who had been previously treated 1 2 lines chemotherapy were randomly assigned (2:1) to either (physician’s choice chemotherapy). Exploratory efficacy safety, using primary analysis data cutoff (Jan 11, 2022), conducted for 0-10%. 110 included (ER n = 58; 1-10% 52). Efficacy results are shown table. longer PFS (median PFS, 8.4 months 2.6 TPC; hazard ratio, 0.24 [95% CI, 0.12-0.48]) OS (hazard 0.35 0.16-0.75]) TPC. 0-10% pts, most common any-grade treatment-emergent adverse events (TEAEs; ≥20% arm) nausea, vomiting, fatigue, decreased appetite, alopecia, constipation, anemia, diarrhea, transaminases increased, white blood cell count decreased, neutrophil decreased. 40 (53.3%) 24 (75.0%) groups, respectively, experienced grade ≥3 TEAEs. Table: 192MOEfficacy subgroupsT-DXdTPCER 0%1n 40n 18PFS, median (95% CI), months8.5 (4.3-11.7)2.9 (1.4-5.1)OS, months18.2 (13.6-NE)8.3 (5.6-20.6)cORR, % CI)50 (33.8-66.2)16.7 (3.6-41.4)ER 1-10%n 35n 17PFS, months8.4 (5.6-12.2)2.6 (1.2-4.6)OS, months20.0 (13.5-NE)10.2 (7.8-14.5)cORR, CI)57.1 (39.4-73.7)5.9 (0.1-28.7)CI, confidence interval; cORR, confirmed objective response rate; NE, not evaluable.1Reported as receptor-negative cohort Modi S et al. N Engl J Med. 2022;387:9-20. Open table new tab evaluable. 1Reported Efficacy, including survival, over was consistent outcomes observed mBC. safety subgroup manageable analysis.