Estimation of the Prevalence of HER2 Low and Describe the SoC, Treatment Patterns, and Outcome in Real-world Practice Among Unresectable and/or Metastatic Breast Cancer Patients With HER2 Low Status

Completed

• Conditions: Breast Cancer
• Interventions: Other: None (Observational study)

• Registration Number: NCT04807595
• Lead Sponsor: AstraZeneca

Brief Summary

This is a worldwide, multicenter, non-interventional, retrospective study of patient medical records from metastatic breast cancer (mBC) patients previously identified as human epidermal growth factor receptor 2 negative (HER2-neg), regardless of hormone status.

Detailed Description

This is a worldwide, multicenter, non-interventional, retrospective study. The study will consist of 2 components. The first component involves local lab rescoring of qualified historical HER2 fixed tissue immunohistochemistry (IHC) stained slides (preferably using Ventana 4B5 assay) at sites (post-training) for mBC patients previously identified as HER2-neg, and independent central retesting of HER2 status using Ventana 4B5 assay for any enrolled patients with available archived tissue samples at designated central laboratories. Local lab rescoring and independent central retesting/local lab retesting will be conducted blinded of historical HER2 IHC scores.

The second component involves linking the rescored IHC status to the patient medical record either through registry databases or patient chart review. Such information will be used to describe the patient demographics, histopathological features, clinical presentation, and treatment patterns following mBC diagnosis, and clinical outcomes in real-world settings for all patients with HER2 scores of 0, \>0 and \< 1+, and 1+2+/ISH- (HER2 low). The clinicopathological and other relevant BC biomarker information will also be examined based on historical biomarker testing results and/or new testing conducted as part of this study.

Study Timeline

• Study First Submitted: 2021-03-18
• Study First Submitted QC: 2021-03-18
• Study First Posted: 2021-03-19
• Study Start: 2021-05-28
• Primary Completion: 2022-04-26
• Study Completion: 2022-04-26
• Status Verified: 2023-02
• Last Update Submitted: 2023-03-03
• Last Update Posted: 2023-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 798

Inclusion Criteria

1. Men or women:

   1. ≥ 18 years of age when consent provided for future sample and clinical data use - applicable for all countries participating in the study except Japan
   2. ≥ 20 years of age when consent provided for future sample and clinical data use - applicable for Japan only

2. Must have a histological or cytological confirmed diagnosis of unresectable or/and mBC between 01 January 2015 and 31 December 2017

3. Must have provided written consent allowing for data and samples to be used in the future and this study would be covered by the consent for future use. If the patient is deceased, a waiver may be accepted

4. Diagnosed as HER2-neg (HER2 IHC 0, 1+, 2+/ISH-), regardless of hormone status

5. Progressed on any systemic anti-cancer therapy (eg, endocrine therapy, chemotherapy, CDK4/6i, targeted therapies other than anti-HER2, or immunotherapy) in the metastatic setting

6. Must have historical HER2 fixed tissue IHC stained slides (preferably stained using Ventana 4B5 assay) in acceptable quality for accurate rescoring.

Exclusion Criteria

1. Have a history of other malignancies, other than basal cell carcinoma of the skin and squamous cell carcinoma of the skin
2. Patients with historical HER2 status of IHC 2+/ISH+ or 3+, or HER2 amplified.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Retrospective cohort	None (Observational study)	Patients with confirmed diagnosis of HER2-neg, unresectable and/or mBC regardless of hormone status dating back from 31 December 2017 - but no older than 01 January 2015 - who progressed on any systematic anti-cancer therapy will be involved in this study.

Primary Outcome Measures

Name	Time	Method
Disease outcome: Time to treatment failure (TTF)	Retrospective: From 01 January 2015 to 31 December 2020	To compare TTF between HER2 low BC patients and the HER2 IHC zero patient population. TTF is defined as the length of time from initiation of treatment to premature discontinuation.
Prevalence/Incidence of HER2 low among HER2-neg mBC patients, based on rescoring of historical HER2 fixed tissue IHC stained slides by Ventana 4B5 assay	Retrospective: From 01 January 2015 to 31 December 2020	To describe the overall prevalence and disease burden of HER2 low (IHC 1+, 2+/ISH-) among unresectable and/or mBC patients identified as HER2-neg, based on rescoring of historical HER2 fixed tissue IHC stained slides by Ventana 4B5 assay. The prevalence of HER2 low (IHC 1+, 2+/ISH-) at unresectable/metastatic BC diagnosis, determined based on rescoring of historical HER2 IHC slides locally, among patients confirmed to be HER2-neg (HER2 IHC zero and HER2 IHC 1+ and 2+/ISH-) by rescoring of historical HER2 IHC slides, will be calculated by the following, based on the re-established HER2 status determined for each patient: Prevalence of HER2 low = (Number of patients with HER2 low)/(Total number of HER2 negative patients )
Disease outcome: Time to first subsequent treatment (TFST)	Retrospective: From 01 January 2015 to 31 December 2020	To compare TFST between HER2 low BC patients and the HER2 IHC zero patient population. TFST is defined as the length of time from the initiation of treatment to the initiation of the patient's next systemic treatment.
Disease outcome: Overall survival (OS)	Retrospective: From 01 January 2015 to 31 December 2020	To compare OS between HER2 low BC patients and the HER2 IHC zero patient population. OS is defined as the length of time from the initiation of treatment that patients are still alive.

Secondary Outcome Measures

Name	Time	Method
Prevalence of HER2 low among unresectable and/or mBC patients identified as HER2-neg based on other IHC assays	Retrospective: From 01 January 2015 to 31 December 2020	To describe HER2 low prevalence among unresectable and/or mBC patients identified as HER2-neg based on other IHC assays, compared with Ventana 4B5 assay.
Concordance of HER2 rescore with historical HER2 score	Retrospective: From 01 January 2015 to 31 December 2020	The concordance between historical HER2 IHC scores and local lab rescoring in the HER2-neg region (IHC score zero, 1+, and 2+) will be characterized.; The concordance between historical scoringHER2 IHC scores and independent central retesting of HER2 IHC status in the HER2-neg region will be assessed using Cohen's Kappa statistics to assess agreement beyond chance alone. By convention, Kappa equal or greater than 0.8 is often considered almost perfect agreement, Kappa between 0.8 and 0.6 is considered substantial agreement.
Prevalence of HER2 low in HR-positive and HR-negative population	Retrospective: From 01 January 2015 to 31 December 2020	The overall prevalence of HER2 low among unresectable and/or mBC patients identified as HER2-neg, regardless of assays used, will be summarized descriptively for HR-positive and HR-negative population, respectively.
Clinicopathological characteristics in patients with HER2 low BC	Retrospective: From 01 January 2015 to 31 December 2020	HER2 low disease will be assessed using descriptive statistics of histopathological and clinicopathological characteristics. A comparison will be made with the HER2 IHC zero patient population.

Trial Locations

Locations (1)

Research Site; 🇬🇧 Manchester, United Kingdom