236P Subgroup analysis by disease history and prior treatments of patients (pts) with HER2-positive (HER2+) metastatic breast cancer (MBC) from DESTINY-Breast03, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1)

Abstract

T-DXd showed superior progression-free survival (PFS) vs T-DM1 (HR, 0.28; 95% CI, 0.22-0.37), with manageable safety, in pts with HER2+ MBC in DESTINY-Breast03 (NCT03529110; Cortes 2022). We present additional patient subgroups by disease history and prior treatment. Pts with HER2+ MBC whose disease had progressed on or after trastuzumab and a taxane were randomized 1:1 to receive T-DXd or T-DM1. An exploratory analysis was conducted of subgroups based on presence of de novo (stage IV disease at initial diagnosis) or recurrent (diagnosed at early stage, developed metastatic disease later) MBC, early progression (disease progression within 6 months [mo] after [neo]adjuvant therapy [12 mo for pertuzumab-containing regimens]), and number and type of prior treatments. PFS (by BICR, data cutoff May 21, 2021) benefit was observed with T-DXd vs T-DM1 for both pts with de novo (HR, 0.35) and recurrent (HR, 0.28) MBC (table). Confirmed objective response rates were consistent between de novo (T-DXd, 79.6% [95% CI, 69.9-87.2] vs T-DM1, 33.7% [24.7-43.6]) and recurrent (T-DXd, 79.8% [72.9-85.6] vs T-DM1, 34.6% [27.2-42.5]) MBC. Within the subgroup of pts with recurrent MBC, there were 35 early progressors (T-DXd, n = 15; T-DM1, n = 20); in a sensitivity analysis, PFS (HR, 0.19; 95% CI, 0.05-0.71) was consistent with the primary analysis. PFS benefit for T-DXd vs T-DM1 was observed regardless of the number of prior lines of anti-HER2 therapy (HR, 0.33 for 1 prior line and HR, 0.23 for ≥2 lines). The safety profile of the subgroups was consistent with the primary analysis.Table: 236PPFS by Disease History, Prior TherapyT-DXdMedian PFS (95% CI), moT-DM1Median PFS (95% CI), moT-DXd vs T-DM1nnHR (95% CI)All pts261NE (18.5-NE)2636.8 (5.6-8.2)0.28 (0.22-0.37)De novo MBC9322.4 (15.0-NE)1045.8 (4.2-8.1)0.35 (0.23-0.53)Recurrent MBC168NE (18.5-NE)1597.0 (5.4-9.7)0.28 (0.20-0.39)Setting of prior systemic therapy in pts with 1 line in metastatic setting excluding hormone therapyMetastatic115NE (15.6-NE)1037.0 (5.4-9.8)0.34 (0.23-0.51)(Neo)adjuvant (early progressors)15NE (12.4-NE)208.2 (5.4-NE)0.19 (0.05-0.71)Lines of prior anti-HER2 therapy1193NE (18.5-NE)1978.0 (5.7-9.7)0.33 (0.24-0.45)≥26622.2 (16.8-NE)634.2 (2.8-5.7)0.23 (0.13-0.38) Open table in a new tab In this exploratory analysis, a benefit of T-DXd vs T-DM1 was observed irrespective of disease history and prior treatment, consistent with the results of the overall primary analysis. T-DXd had a manageable safety profile.