217O Patient-reported outcomes (PROs) from DESTINY-Breast04, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician's choice (TPC) in patients (pts) with HER2-low metastatic breast cancer (MBC)

Abstract

DESTINY-Breast04 (NCT03734029) showed improvement in progression-free and overall survival of T-DXd vs TPC in pts with HER2-low MBC regardless of hormone receptor status, with no new safety signals. Here we report PROs on the effect of treatment on health-related quality of life (QOL) of T-DXd vs TPC in the hormone receptor–positive cohort. Pts with centrally confirmed HER2-low (IHC1+ or IHC2+/ISH-) MBC with 1-2 prior lines of chemotherapy in the metastatic setting were assigned 2:1 to T-DXd (Q3W) or TPC (Q3W or Q4W). PROs were measured using the European Organization for Research and Treatment of Cancer QOL questionnaires (EORTC QLQ-C30, primary variable: global health status [GHS]/QOL scale score, and EORTC QLQ-BR23) and the EuroQol 5-dimension, 5-level (EQ-5D-5L) visual analog scale (VAS). PROs were assessed at prespecified timepoints per the protocol. Change from baseline (CFB) and time to definitive deterioration (TDD) were assessed. Deterioration was defined as an increase of ≥10 points. In both arms, compliance for questionnaires was >92% at baseline and >80% for cycles 2-27. Baseline GHS score was 36.3 for T-DXd and 37.8 for TPC. Mean CFB for GHS/QOL of the QLQ-C30 remained stable (within ± 10 points) over time for pts in the T-DXd arm (n=331) up to 27 cycles and TPC arm (n=163) up to 13 cycles; beyond these cycles, the number of pts on treatment (n<10%) was too low to be informative. Median TDD of QLQ-C30 GHS/QOL was 7.6 mo for T-DXd vs 5.1 mo for TPC (hazard ratio [HR], 0.71 [95% CI, 0.56-0.92]), and all prespecified QLQ-C30 subscales had longer TDD with T-DXd, including pain (HR, 0.51 [95% CI, 0.39-0.65]) and physical functioning (HR, 0.54 [95% CI, 0.42-0.70]). For breast-specific arm symptoms of the QLQ-BR23, median TDD was 9.8 mo for T-DXd vs 5.4 mo for TPC (HR, 0.67 [95% CI, 0.50-0.88]). Median TDD of EQ-5D-5L VAS was 8.8 mo for T-DXd vs 4.7 mo for TPC (HR, 0.70 [0.54-0.91]). Pts who received T-DXd maintained GHS/QOL longer than TPC in all prespecified QLQ-C30 subscales while on therapy. These results are consistent with the primary results and confirm the QOL benefit of T-DXd vs TPC for pts with HER2-low MBC.