Patient-reported outcomes with trastuzumab deruxtecan in hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer: results from the randomized DESTINY-Breast06 trial

BACKGROUND: The randomized phase III DESTINY-Breast06 trial (NCT04494425) demonstrated superior efficacy with trastuzumab deruxtecan (T-DXd) versus chemotherapy treatment of physician's choice (TPC) and no new safety signals in patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-low immunohistochemistry (IHC) 1+, IHC 2+/in situ hybridization-negative, and HER2-ultralow (IHC 0 with membrane staining) metastatic breast cancer (mBC). Here, we report the patient-reported outcome (PRO) endpoints in the intent-to-treat (ITT; HER2-low/-ultralow) and HER2-low populations. PATIENTS AND METHODS: Patients with progressive disease (PD) after one or more prior lines of endocrine-based therapy and no prior chemotherapy for mBC were assigned 1 : 1 to T-DXd 5.4 mg/kg once every 3 weeks (n = 436) or TPC n = 430; 59.8% capecitabine; 24.4% nab-paclitaxel; and 15.8% paclitaxel. PRO questionnaires included the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and breast cancer-specific module (EORTC QLQ-BR45). Changes from baseline (CFB; earliest of 31 weeks or on-study PD) and time to deterioration were assessed. RESULTS: The median treatment duration was 11.0 (T-DXd) versus 5.6 (TPC) months. In the ITT, the mean CFB scores were similar across treatments in EORTC QLQ-C30 global health status/quality of life (QOL) and functioning scales. T-DXd was associated with less pain adjusted mean difference -7.2, 95% confidence interval (CI) -9.9 to -4.5 and fewer skin/mucosal symptoms (adjusted mean difference -9.5, 95% CI -11.5 to -7.5), but more nausea/vomiting (adjusted mean difference 7.2, 95% CI 5.3-9.2), appetite loss (adjusted mean difference 6.8, 95% CI 3.6-10.0), and constipation (adjusted mean difference 5.5, 95% CI 2.6-8.4) versus TPC. T-DXd reduced the risk of clinically meaningful deterioration in physical/role/emotional functioning, pain, and fatigue versus TPC, but increased the risk of deterioration in gastrointestinal symptoms. Results were similar in the HER2-low population. CONCLUSIONS: T-DXd preserved QOL while delaying deterioration in physical/role/emotional functioning, pain, and fatigue versus TPC, albeit with more gastrointestinal symptoms. PRO data complement the efficacy/safety of T-DXd in this population.