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

Recruiting

• Conditions: Breast Cancer

• Registration Number: NCT06727227
• Lead Sponsor: AstraZeneca

Brief Summary

A longitudinal, non-interventional study with trastuzumab deruxtecan for patients with HER2-low expressing unresectable or metastatic breast cancer in Bulgaria and Slovenia

Detailed Description

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).

Study Timeline

• Study First Submitted: 2024-11-20
• Study First Submitted QC: 2024-12-06
• Study First Posted: 2024-12-10
• Study Start: 2025-01-29
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-28
• Primary Completion: 2027-03-31
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

• Adult patient (age ≥18 years) with histological or cytological confirmed diagnosis of unresectable or mBC.
• Documented HER2-low status (IHC1+, IHC2+/ISH-) in patients who have received prior chemotherapy in the metastatic setting or documented HER2-low status (IHC 1+, IHC 2+/ISH-) in patients who have developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.
• Recent prior decision to initiate therapy of T-DXd per SmPC (up to 30 days). Documentation confirming this decision will be required and collected.
• Able and willing to provide informed consent.

Exclusion Criteria

• Pregnancy or breastfeeding.
• History of other primary malignancies in 2 years prior to unresectable or mBC diagnosis.
• Patients who at time of data collection for this study are participating in or have participated in an interventional study that remains blinded.
• HER2-low status patients who have previously documented HER2+ status in the same tumor.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Real-world Time to Next Treatment (rwTTNT1, median, 95% CI, measured in months)	Baseline up to 19 months	The duration from initiation of trastuzumab deruxtecan (T-DXd) treatment to the start of the subsequent therapy or death from any cause, whichever occurs first, assessed up to 19 months.

Secondary Outcome Measures

Name	Time	Method
Describe type and proportion of previous treatments for unresectable or mBC and comorbidities	Baseline	Prior treatments: surgery, chemotherapy, radiotherapy, therapies in neoadjuvant/adjuvant/advanced setting; treatment line (special focus should be given on endocrine and chemotherapy recycling in the metastatic setting). The timeline for these treatments will include all therapies administered from the time of breast cancer diagnosis.
Duration of previous treatments and number of treatment lines	Baseline	Start and stop date, if available
Response to previous treatments	Baseline	To describe patients' response to previous treatment, as applicable: clinical response (partial response/complete response/stable disease/disease progression; if progression: date and site of progression)
Mean (SD) age at diagnosis	Baseline	Describe the patients' mean (SD) age at diagnosis
Mean (SD) age at T-DXd start	Baseline	To describe patients' mean (SD) age at T-DXd start
Proportion of males and females	Baseline	To describe the proportion of males and females
Proportion of patients with HR+ vs HR- tumors	Baseline	Describe the proportion of patients with HR+ vs HR- tumors
Distribution by smoking status	Baseline	Describe the patients' smoking status. Includes electronic cigarettes/vapes
Type and proportion of comorbidities	Baseline	Comorbidities (including cardiovascular diseases, pulmonary disorders, hepatic disorders, renal disorders, blood and lymphatic system disorders, metabolism and nutrition disorders, gastrointestinal disorders, hepatobiliary disorders, central nervous system \[CNS\] disorders, eye disorders, skin disorders and musculoskeletal and connective tissue disorders, infections and infestations and other relevant
Distribution by ECOG status	Baseline	Describe patients' ECOG PS at index date
mean (SD) duration of disease (at index), measured in months or years	Baseline	Describe patients' mean duration of disease through date of initial diagnosis and date of diagnosis of unresectable or metastatic breast cancer, as applicable
HER2-low status and type and proportion of metastatic sites	Baseline	Describe patients' HER2-low status and type and proportion of metastatic sites through most recent HER2-low status, new metastatic sites since the time of mBC diagnosis, disease burden (all disease sites, including the presence/absence of brain metastases \[stable/active\]
rwTTNT1 by Number of Prior of Therapy Lines for Metastatic Disease (median, 95% CI, measured in months, 1 vs 2 vs 3+ Lines)	Baseline up to 19 months	Describe rwTTNT1 stratified by the number of prior therapy lines in the metastatic setting.
rwTTNT1 by HR-status (median, 95% CI, measured in months, HR+ vs HR-)	Baseline up to 19 months	Describe rwTTNT1 stratified by hormone receptor (HR) status.
Real-world Time to Treatment Discontinuation (rwTTD1, median, 95% CI, measured in months)	Baseline up to 19 months	Evaluate the duration from the start of T-DXd treatment until its discontinuation or death, whichever occurs first.

Trial Locations

Locations (1)

Research Site; 🇸🇮 Maribor, Slovenia