Real-world Study of Trastuzumab Deruxtecan in Patients With Unresectable or Metastatic HER2-low Breast Cancer

EXPLORE Non-Interventional Study for HER2-low Breast Cancer Treatment with T-DXd

Background:

HER2 is a prognostic marker in various cancers, including breast cancer (BC). Traditionally categorized as HER2-positive or HER2-negative, recent advancements with anti-HER2 ADCs, like trastuzumab deruxtecan (T-DXd), have shown benefits for HER2-low status BC. The DB-04 trial demonstrated significant survival benefits with T-DXd, leading to its EMA approval for HER2-low BC in January 2023.

Study Rationale:

Limited real-world evidence exists for T-DXd in HER2-low BC, particularly in the Balkans. The EXPLORE study aims to fill this gap by collecting real-world data in Bulgaria and Slovenia.

Objectives:

Primary Objective:

Describe real-world Time to Next Treatment (rwTTNT1) of T-DXd in HER2-low unresectable or metastatic BC (mBC).

Secondary Objectives:

Describe pre-T-DXd treatment patterns at baseline. Describe patient demographics and clinical characteristics at baseline. Describe rwTTNT1 by prior therapy lines in the metastatic setting and by hormone receptor (HR) status.

Evaluate real-world Time to Treatment Discontinuation (rwTTD1).

Exploratory Objectives:

Evaluate real-world progression-free survival (rwPFS1). Characterize subsequent treatments and post-progression endpoints (rwTTNT2, rwTTD2, rwPFS2).

Describe biopsy patterns. Evaluate reasons for discontinuation (rwTTNT1 and rwTTNT2). Describe T-DXd treatment changes over time. No formal hypothesis is set.

Methods:

Study Design:

Observational, longitudinal, non-interventional study in Bulgaria and Slovenia. Patients with unresectable or mBC starting T-DXd within 30 days of enrolment. Data from hospital charts at routine visits.

Population:

Adults (≥18 years) with HER2-low mBC, initiating T-DXd independent of the study.

Exposure:

T-DXd treatment details (dose, duration) and other therapies recorded. Recommended T-DXd dose: 5.4 mg/kg IV every 3 weeks.

Outcomes:

Primary: Time from T-DXd initiation to subsequent therapy or death. Exploratory: Various survival measures, biopsy patterns, reasons for discontinuation, and treatment changes.

Sample Size:

Approximately 135 patients (100 in Bulgaria, 35 in Slovenia).

Statistical Analysis:

Descriptive analyses for cohort characteristics. Kaplan-Meier method for time-to-event endpoints. Subgroup analyses by prior therapy lines and HR status.

Data Collection:

Data from paper or electronic health records. Single anonymized dataset via electronic case report forms (CRFs).

• Describe type and proportion of previous treatments for unresectable or mBC and comorbidities [Time frame: Baseline]
• Duration of previous treatments and number of treatment lines [Time frame: Baseline]
• Response to previous treatments [Time frame: Baseline]
• Mean (SD) age at diagnosis [Time frame: Baseline]
• Mean (SD) age at T-DXd start [Time frame: Baseline]
• Proportion of males and females [Time frame: Baseline]
• Proportion of patients with HR+ vs HR- tumors [Time frame: Baseline]
• Distribution by smoking status [Time frame: Baseline]
• Type and proportion of comorbidities [Time frame: Baseline]
• Distribution by ECOG status [Time frame: Baseline]
• mean (SD) duration of disease (at index), measured in months or years [Time frame: Baseline]
• HER2-low status and type and proportion of metastatic sites [Time frame: Baseline]