186O Patient-reported outcomes (PROs) from DESTINY-Breast02, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2–positive (HER2+) metastatic breast cancer (mBC)

In DESTINY-Breast02 (NCT03523585), T-DXd improved progression-free and overall survival vs TPC in pts with HER2+ mBC who were resistant/refractory to trastuzumab emtansine (T-DM1) (Krop et al. SABCS 2022). Here, we report data on PROs and health-related quality of life (QoL). Pts with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization amplified) T-DM1–resistant/refractory mBC were assigned 2:1 to T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine). PROs were collected and measured at prespecified timepoints using the European Organization for Research and Treatment of Cancer QoL questionnaires (EORTC QLQ)-C30, the breast-cancer–specific EORTC QLQ-BR45 (scored as EORTC QLQ-BR23), and the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analog scale. Change from baseline (CFB) and time to definitive deterioration (TDD) were assessed. QLQ-C30 global health status (GHS)/QoL score was the primary variable of interest. In the T-DXd (n = 406) and TPC (n = 202) arms (median treatment duration of the safety analysis set: 11.3 vs ∼4.5 mo), questionnaire compliance was >92% at baseline and >76% at cycles 3-29. Mean CFB of GHS/QoL remained stable (within ±10 points) up to cycle 39 for T-DXd and cycle 21 for TPC, after which the number of pts on treatment was not informative (n < 10%). Median TDD was longer with T-DXd vs TPC for GHS/QoL (14.1 vs 5.9 mo; HR, 0.56 [95% CI, 0.44-0.71]) and for all measured QLQ-C30 subscales, including physical functioning (18.7 vs 6.8 mo; HR, 0.46 [95% CI, 0.36-0.60]) and pain (18.7 vs 5.8 mo; HR, 0.38 [95% CI, 0.29-0.49]), with the exception of nausea/vomiting (5.7 vs 6.1 mo; HR, 1.09 [95% CI, 0.86-1.39]). With T-DXd vs TPC, pts experienced prolonged TDD on the QLQ-BR23 arm symptom subscale (18.3 vs 8.8 mo; HR, 0.57 [95% CI, 0.44-0.75]). Mean CFB in GHS/QoL suggested that overall health and QoL were maintained in T-DXd-treated pts. TDD was longer on all measured QLQ-C30 subscales, except for nausea/vomiting, for pts receiving T-DXd vs TPC. These results continue to support the benefit of T-DXd in pts with T-DM1–resistant HER2+ mBC.