Observational Study into Treatment Patterns, Safety Management, and Effectiveness of T-DXd in Patients with HER2-positive Metastatic Breast Cancer in Europe and Canada: SMART EUCAN

Objectif(s) de la recherche et intérêt pour la santé publique

Finalité de l'étude

Objectifs poursuivis

Domaines médicaux investigués

Bénéfices attendus

ENHERTU (trastuzumab deruxtecan; T‑DXd) has demonstrated strong efficacy in HER2‑positive metastatic breast cancer (HER2+ mBC), particularly in the DESTINY‑Breast03 trial. However, safety concerns—especially treatment‑emergent adverse events (TEAEs) such as nausea, hematologic toxicity, fatigue, and interstitial lung disease (ILD)—have led some clinicians to delay its use or apply varied management strategies. In clinical trials, TEAEs frequently resulted in dose interruptions (44%), dose reductions (28%), and treatment discontinuation (23%), with ILD/pneumonitis being the leading cause of discontinuation.
Real‑world studies show similar patterns: approximately 26–32% of patients required dose reductions due to adverse events, while discontinuation was less common and mainly driven by ILD. These findings highlight the need for better understanding of T‑DXd safety management in routine clinical practice.
The SMART program was established to address this evidence gap through real‑world data. It includes regional studies in Europe and Canada (SMART EUCAN) and the United States (SMART USA) to evaluate treatment patterns, real‑world adverse events (rwAEs), and their management in patients with HER2+ mBC treated with T‑DXd.
SMART EUCAN is a retrospective observational chart‑review study conducted across oncology centers in the UK, France, Spain, and Canada. It will include up to 625 patients who initiated T‑DXd in the second or later line of metastatic therapy between 2022 and 2025. The primary objective is to describe T‑DXd treatment patterns, including dose modifications, interruptions, and discontinuation. Secondary objectives include characterizing patient demographics and clinical features, time to treatment modification or discontinuation, reasons for treatment changes, incidence and timing of rwAEs, and treatment patterns following rwAE occurrence. An exploratory objective will assess real‑world progression‑free survival in patients receiving T‑DXd as second‑line therapy following standard first‑line THP.
Overall, results from the SMART EUCAN and SMART USA studies will provide practical insights into real‑world safety management, treatment sequencing, and outcomes with T‑DXd, supporting best practices and reinforcing evidence that earlier use of T‑DXd may maximize clinical benefit for patients with HER2+ mBC.