Clinical trial NCT06727227: Real-world Study of Trastuzumab Deruxtecan in Patients With Unresectable or Metastatic HER2-low Breast Cancer
Official title: REal-world Study of Trastuzumab deruXtecan in Patients With unresectabLe or Metastatic Breast Cancer Expressing HER2-lOw From BulgaRia and SlovEnia (EXPLORE)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-12-10
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Real-world Time to Next Treatment (rwTTNT1, median, 95% CI, measured in months)
timeFrame: Baseline up to 19 months
Secondary outcomes:
measure: Describe type and proportion of previous treatments for unresectable or mBC and comorbidities
timeFrame: Baseline
measure: Duration of previous treatments and number of treatment lines
timeFrame: Baseline
measure: Response to previous treatments
timeFrame: Baseline
measure: Mean (SD) age at diagnosis
timeFrame: Baseline
measure: Mean (SD) age at T-DXd start
timeFrame: Baseline
measure: Proportion of males and females
timeFrame: Baseline
measure: Proportion of patients with HR+ vs HR- tumors
timeFrame: Baseline
measure: Distribution by smoking status
timeFrame: Baseline
measure: Type and proportion of comorbidities
timeFrame: Baseline
measure: Distribution by ECOG status
timeFrame: Baseline
measure: mean (SD) duration of disease (at index), measured in months or years
timeFrame: Baseline
measure: HER2-low status and type and proportion of metastatic sites
timeFrame: Baseline
measure: rwTTNT1 by Number of Prior of Therapy Lines for Metastatic Disease (median, 95% CI, measured in months, 1 vs 2 vs 3+ Lines)
timeFrame: Baseline up to 19 months
measure: rwTTNT1 by HR-status (median, 95% CI, measured in months, HR+ vs HR-)
timeFrame: Baseline up to 19 months
measure: Real-world Time to Treatment Discontinuation (rwTTD1, median, 95% CI, measured in months)
timeFrame: Baseline up to 19 months
Other outcomes:
measure: Real-world Progression-Free Survival (rwPFS1, median, 95% CI, measured in months)
timeFrame: Baseline up to 19 months
measure: Real-world Time to Second Next Treatment (rwTTNT2, median, 95% CI, in months)
timeFrame: Baseline up to 19 months
measure: Real-world Time to Subsequent Treatment Discontinuation (rwTTD2, median, 95% CI, measured in months)
timeFrame: Baseline up to 19 months
measure: Real-world progression free survival 2 (rwPFS2, median, 95% CI, measured in months)
timeFrame: Baseline up to 19 months
measure: Biopsy Patterns (number of biopsies conducted prior to the start of T-DXd treatment)
timeFrame: Baseline, assessed for the past 10 years
measure: Biopsy Patterns (the time from the last fresh biopsy to the start of T-DXd treatment, measured in months or years)
timeFrame: Baseline, assessed for the past 10 years
measure: Reasons for Discontinuation (rwTTNT1 and rwTTNT2)
timeFrame: Baseline up to 19 months
measure: T-DXd Treatment Changes Over Time
timeFrame: Baseline up to 19 months
Locations:
city: Panagyurishte
country: Bulgaria
facility: Research Site
state: Pazardzhik
city: Burgas
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Stara Zagora
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Ljubljana
country: Slovenia
facility: Research Site
city: Maribor
country: Slovenia
facility: Research Site
Study officials:
References: