Patient-reported outcomes from DESTINY-Breast04: trastuzumab deruxtecan versus physician’s choice of chemotherapy in patients with HER2-low mBC

Background: The phase 3 DESTINY-Breast04 trial demonstrated superior efficacy and acceptable safety with trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy in previously treated patients with human epidermal growth factor receptor 2 (HER2)–low metastatic breast cancer (mBC). We report the patient-reported outcomes (PROs), focusing on the hormone receptor–positive cohort. Patients and Methods: Patients were randomized 2:1 to T-DXd (5.4 mg/kg intravenously every 3 weeks) or physician’s choice of chemotherapy and prospectively assessed for PRO measures. Change from baseline and time to definitive deterioration (TDD) were calculated from the EORTC QLQ-C30 and QLQ-BR45 and the EQ-5D-5L questionnaires. Results: Baseline global health status/quality of life (GHS/QoL) scores were similar between groups (T-DXd, 331 patients; physician’s choice, 163 patients); there were no clinically meaningful changes while on either treatment (median duration: T-DXd, 8.2 months; physician’s choice, 3.5 months). Median TDD for GHS/QoL was delayed with T-DXd vs physician’s choice (11.4 vs 7.5 months, respectively; hazard ratio, 0.69; 95% CI, 0.52-0.92). Median TDD for all prespecified PROs, including pain, favored T-DXd. In an additional analysis, the median TDD was shorter for nausea and vomiting with T-DXd vs the physician’s choice. Conclusions: Trastuzumab deruxtecan maintained GHS/QoL scores despite a longer treatment course compared with standard chemotherapy and delayed definitive deterioration across all prespecified PROs vs the physician’s choice. Appropriate management of adverse events and use of preventive measures (ie, antiemetic prophylaxis) may further support patient health-related quality of life. These findings reinforce the benefit of T-DXd as an option for patients with HER2-low mBC. ClinicalTrials.gov: