Breast CancerNCT04807595
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
An observational study of Breast Cancer, run by AstraZeneca at 13 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Breast Cancer
- What is being tested?
- None (Observational study)
- How many people
- 798 participants
- Where
- 13 sitesin 10 countries
- Study dates
- 28 May 2021to 26 Apr 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients will be eligible for study inclusion if their mBC diagnosis date is between 01 January 2015 and 31 December 2017 (dating back from 31 December 2017 but no older than 01 January 2015).
Who may be able to join
- Men or women:
- ≥ 18 years of age when consent provided for future sample and clinical data use - applicable for all countries participating in the study except Japan
- ≥ 20 years of age when consent provided for future sample and clinical data use - applicable for Japan only
- Must have a histological or cytological confirmed diagnosis of unresectable or/and mBC between 01 January 2015 and 31 December 2017
- 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
- Diagnosed as HER2-neg (HER2 IHC 0, 1+, 2+/ISH-), regardless of hormone status
- 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
- Must have historical HER2 fixed tissue IHC stained slides (preferably stained using Ventana 4B5 assay) in acceptable quality for accurate rescoring.
Who cannot join
- Have a history of other malignancies, other than basal cell carcinoma of the skin and squamous cell carcinoma of the skin
- Patients with historical HER2 status of IHC 2+/ISH+ or 3+, or HER2 amplified.
Trial locations and contacts
13 sites in 10 countries.
13 sites in 10 countries
Japan3 sites
Research Site
Chūōku, 104-8560
Research Site
Fukuoka, 811-1395
Research Site
Isehara, 259-1193
About this study
Official title: A Multicenter Study to Estimate 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 - the RetroBC-HER2L Study
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- None (Observational study)
- Keywords
- Metastatic breast cancer, Retrospective study, Epidemiology study, Human epidermal growth factor receptor 2 negative, Human epidermal growth factor receptor 2 low
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
None (Observational study)Other
Also called Observational study
The data source for this project will be HER2 IHC historical scores, local lab rescoring of historical HER2 fixed tissue slides, independent central retesting or local lab retesting (under special occasions) of HER2 IHC status for enrolled patients who have available tissue, other biomarker testing results based on historical testing and/or testing of archived tissue samples when available, and curated patient-level data. Real-world data sources include electronic health records/electronic medical records (EHR/EMR) and biobank registries. Data from EHR/EMR sources will be curated. Biobank tissue for enrolled patients who have multiple samples available will be selected consecutively when possible and will start with the latest available samples then move backward in time.
| Study group | Role | What they receive |
|---|---|---|
| Retrospective cohort | 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. Receives: Other: None (Observational study) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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 )
Measured: Retrospective: From 01 January 2015 to 31 December 2020
Disease outcome: Time to first subsequent treatment (TFST)
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.
Measured: Retrospective: From 01 January 2015 to 31 December 2020
Disease outcome: Time to treatment failure (TTF)
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.
Measured: Retrospective: From 01 January 2015 to 31 December 2020
Disease outcome: Overall survival (OS)
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.
Measured: Retrospective: From 01 January 2015 to 31 December 2020
Secondary outcomes (4)
Clinicopathological characteristics in patients with HER2 low BC
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.
Measured: Retrospective: From 01 January 2015 to 31 December 2020
Concordance of HER2 rescore with historical HER2 score
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.
Measured: Retrospective: From 01 January 2015 to 31 December 2020
Prevalence of HER2 low among unresectable and/or mBC patients identified as HER2-neg based on other IHC assays
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.
Measured: Retrospective: From 01 January 2015 to 31 December 2020
Prevalence of HER2 low in HR-positive and HR-negative population
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.
Measured: Retrospective: From 01 January 2015 to 31 December 2020
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start28 May 2021
- Primary completion26 Apr 2022
- Study completion26 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 798 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04807595
- Sponsor's protocol ID
- D9673R00004
- Status last verified
- Feb 2023
- First submitted
- 18 Mar 2021
- Last updated
- 6 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Viale G, Basik M, Niikura N, Tokunaga E, Brucker S, Penault-Llorca F, Hayashi N, Sohn J, Teixeira de Sousa R, Brufsky AM, O'Brien CS, Schmitt F, Higgins G, Varghese D, James GD, Moh A, Livingston A, de Giorgio-Miller V. Retrospective study to estimate the prevalence and describe the clinicopathological characteristics, treatments received, and outcomes of HER2-low breast cancer. ESMO Open. 2023 Aug;8(4):101615. doi: 10.1016/j.esmoop.2023.101615. Epub 2023 Aug 8.
PubMed 37562195
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Study to Estimate 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 - the RetroBC-HER2L Study
- ClinicalTrials.gov ID
- NCT04807595
- Acronym / sponsor ID
- D9673R00004
- Conditions
- Breast Cancer
- Keywords
- Metastatic breast cancer, Retrospective study, Epidemiology study, Human epidermal growth factor receptor 2 negative, Human epidermal growth factor receptor 2 low
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 798 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Study start
- 28 May 2021 (actual)
- Primary completion
- 26 Apr 2022 (actual)
- Study completion
- 26 Apr 2022 (actual)
- First posted
- 19 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Retrospective cohort | – | Other: 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. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients will be eligible for study inclusion if their mBC diagnosis date is between 01 January 2015 and 31 December 2017 (dating back from 31 December 2017 but no older than 01 January 2015).
Key inclusion criteria (8 listed)
- Men or women:
- Must have a histological or cytological confirmed diagnosis of unresectable or/and mBC between 01 January 2015 and 31 December 2017
- 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
- Diagnosed as HER2-neg (HER2 IHC 0, 1+, 2+/ISH-), regardless of hormone status
- 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
Key exclusion criteria (2 listed)
- Have a history of other malignancies, other than basal cell carcinoma of the skin and squamous cell carcinoma of the skin
- Patients with historical HER2 status of IHC 2+/ISH+ or 3+, or HER2 amplified.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| None (Observational study)Also: Observational studyThe data source for this project will be HER2 IHC historical scores, local lab rescoring of historical HER2 fixed tissue slides, independent central retesting or local lab retesting (under special occasions) of HER2 IHC status for enrolled patients who have available tissue, other biomarker testing results based on historical testing and/or testing of archived tissue samples when available, and curated patient-level data. Real-world data sources include electronic health records/electronic medical records (EHR/EMR) and biobank registries. Data from EHR/EMR sources will be curated. Biobank tissue for enrolled patients who have multiple samples available will be selected consecutively when possible and will start with the latest available samples then move backward in time. | Other | Retrospective cohort |
Primary outcome
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
Time frame: 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)
Time frame: 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: Time to treatment failure (TTF)
Time frame: 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.
Disease outcome: Overall survival (OS)
Time frame: 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.
4 secondary outcomes
Clinicopathological characteristics in patients with HER2 low BC
Time frame: Retrospective: From 01 January 2015 to 31 December 2020
Concordance of HER2 rescore with historical HER2 score
Time frame: Retrospective: From 01 January 2015 to 31 December 2020
Prevalence of HER2 low among unresectable and/or mBC patients identified as HER2-neg based on other IHC assays
Time frame: Retrospective: From 01 January 2015 to 31 December 2020
Prevalence of HER2 low in HR-positive and HR-negative population
Time frame: Retrospective: From 01 January 2015 to 31 December 2020
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2023.
- Derived from this study: PubMed 37562195Viale G, Basik M, Niikura N, Tokunaga E, Brucker S, Penault-Llorca F, Hayashi N, Sohn J, Teixeira de Sousa R, Brufsky AM, O'Brien CS, Schmitt F, Higgins G, Varghese D, James GD, Moh A, Livingston A, de Giorgio-Miller V. Retrospective study to estimate the prevalence and describe the clinicopathological characteristics, treatments received, and outcomes of HER2-low breast cancer. ESMO Open. 2023 Aug;8(4):101615. doi: 10.1016/j.esmoop.2023.101615. Epub 2023 Aug 8.
- CSR Synopsis RedactedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by AstraZeneca at 13 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Japan, Portugal, United States, Australia, Canada and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Retrospective: From 01 January 2015 to 31 December 2020). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04807595, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2023.