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

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).

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 Population:

Criteria:

Age: Adult patients (≥18 years). Diagnosis: Confirmed diagnosis of unresectable or metastatic breast cancer (mBC).

HER2 Status: Documented HER2-low status. Treatment Decision: Patients for whom the decision to initiate trastuzumab deruxtecan (T-DXd) treatment has been made independently and prior to enrolment in the study.

Enrollment:

Timing: Patients must be enrolled within 30 days before the administration of the first T-DXd infusion.

Consent: Patients must provide written informed consent for data collection.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.