Use and outcomes of trastuzumab deruxtecan in HER2-positive and HER2-low metastatic breast cancer in a real-world setting: a nationwide cohort study

Abstract

Background: Since 2020, trastuzumab deruxtecan (T-DXd) has been used in France for patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive or HER2-low metastatic breast cancer (mBC). We aimed to describe the clinical characteristics, outcomes, and potential toxicities among patients receiving T-DXd for HER2-positive and HER2-low mBC.

Patients and methods: Using the French National Health Data System (SNDS), we identified patients who initiated T-DXd for mBC from 30 September 2020 to 30 September 2023. Follow-up data were available through 31 December 2023. Patients were categorized into three groups according to HER2 expression and line of treatment: HER2-positive mBC receiving T-DXd in the third (HER2+ 3L) or second line (HER2+ 2L) and HER2-low mBC receiving T-DXd in the second line (HER2-low2L). We describe their characteristics and report the Kaplan-Meier estimates of overall survival (OS) and incidence of hospitalization.

Results: The cohort comprised 5890 patients, including 2010 (34.1%) HER2+ 3L, 1260 (21.4%) HER2+ 2L, and 2620 (44.5%) HER2-low2L. For the three respective groups, the median age at inclusion was 59 years [interquartile range (IQR) 51-69 years], 59 years (50-68 years), and 61 years (52-70 years); 34.8%, 30.2%, and 16.0% had brain metastases; 14.2%, 13.7%, and 13.4% had a current or history of cardiovascular disease. Median OS was 30.2 months [95% confidence interval (CI) 28.1-33.5 months] for HER2+ 3L patients, was not reached for HER2+ 2L patients, and was 16.8 months (95% CI 14.5 months-not reached) for HER2-low2L patients. The incidence of hospitalization for cardiac, respiratory, digestive, and hematological disorders was similar for HER2-positive patients treated in the second or third line, whereas HER2-low patients had higher incidence rates for these events.

Conclusion: In this large French observational study, T-DXd users were older, had more comorbidities, and had more brain metastases than patients included in registration trials. The rapid expansion of clinical indications of T-DXd calls for proactive surveillance and timely management of potentially life-threatening T-DXd-related toxicity.

Keywords: French National Health Data System (SNDS); early access program; metastatic breast cancer; outcomes; trastuzumab deruxtecan (T-DXd).

Figure 1

Overall survival by medical indication. (A) HER2+ 3L+: HER2-positive patients receiving T-DXd as third-line therapy and beyond, with a history of trastuzumab emtansine. (B) HER2+ 2L+: HER2-positive patients receiving T-DXd as second-line therapy and beyond, with no history of trastuzumab emtansine. (C) HER2-low 2L+: HER2-low patients receiving T-DXd as second-line therapy and beyond. 2L, second-line; 3L, third-line; HER2, human epidermal growth factor receptor 2; mOS, median overall survival; NR, not reached; T-DXd, trastuzumab deruxtecan.