(CSPOT40) Use and Outcomes of Trastuzumab Deruxtecan in HER2-positive and HER2-low Metastatic Breast Cancer in Real-World Setting: A Nationwide Cohort Study

Background: Since 2020, trastuzumab deruxtecan (T-DXd) has been used in France for patients with previously treated HER2-positive or HER2-low metastatic breast cancer (mBC).

Objectives: We aimed to describe clinical characteristics, clinical outcomes, and potential adverse events, including hospitalizations, among patients receiving T-DXd for HER2-positive and HER2-low metastatic breast cancer.

Methods: Using the French National Health Data System (SNDS), we identified patients having initiated T-DXd for mBC from September 30, 2020 to September 30, 2023. Follow-up was available through December 31, 2023. Patients were categorized in three groups according to BC subtype and line of treatment: HER2-positive mBC third-line (HER2+3L) and second-line (HER2+2L), and HER2-low second line (HER2-low2L). The Kaplan-Meier method was used to estimate overall survival (OS) and treatment duration (TTD). The incidences of potential adverse events-related hospitalizations were estimated using a Poisson distribution.

Results: The cohort comprised 5890 patients including 2010 (34.1%) HER2+3L, 1260 (21.4%) in HER2+2L and 2620 (44.5%) in HER2-low2L. For the three respective cohorts, median age at inclusion was 59 (interquartile range, [IQR] 51-69), 59 (50-68) and 61 (52-70); 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 follow-up was 17.0 months (IQR 9.6-24.7) for HER2+3L, 11.1 months (IQR 6.6-15.3) for HER2+2L and 7.3 months (IQR 4.9-10.2) for HER2-low2L.
Median OS was 30.2 months (95% confidence interval [CI]: 28.1-33.5) for HER2+3L patients, was not reached for HER2+2L patients, and was 16.8 months (95% CI: 14.5 – not reached) for HER2-low2L patients.
Incidence of hospitalizations for cardiac, respiratory, digestive and hematologic disorders were similar in HER2+ patients treated in 2L or 3L while HER2-low patients had higher incidence rates for these events.

Conclusions: In this large French study evaluating the use of T-DXd in the real world, T-DXd users were older, more comorbid and had more brain metastases than patients included in registration trials. The rapid expansion of clinical indications of T-DXd, including patients with HER2+ and HER2-low mBC in earlier lines, calls for proactive surveillance and timely management of potentially life-threatening T-DXd-related toxicities.