Periodic Reporting for period 1 - DEFINITIVE (Diagnostic HER2DX-guided treatment for patients with early-stage HER2-positive breast cancer)
Reporting period: 2023-12-01 to 2025-05-31
Despite major advances in the treatment of HER2-positive breast cancer, a significant proportion of patients receive intensive therapies that may not be necessary, leading to avoidable toxicities, reduced quality of life, and increased healthcare costs. Recent scientific progress has opened the door to more personalised treatment strategies, yet the integration of such innovations into clinical practice remains limited due to a lack of robust, prospective clinical validation. The EU-funded DEFINITIVE project addresses this gap by validating the clinical utility of HER2DX, a novel 27-gene expression test specifically designed to guide treatment decisions in early-stage HER2-positive breast cancer. HER2DX has the potential to identify patients who can safely benefit from de-escalated therapies, thereby reducing overtreatment while maintaining excellent survival outcomes. Therefore, the overarching objective of DEFINITIVE is to generate high-quality clinical evidence to support the adoption of HER2DX in routine oncology practice. DEFINITIVE brings together a multidisciplinary consortium of leading European hospitals, cancer research networks, biostatisticians, regulatory experts, as well as patient representatives.
All partners have collaborated in the design and setup of the clinical trial, including the development of the clinical protocol. Notably, the involvement of patient representatives at this early stage has ensured a patient-centred approach to the research. In addition, the selection of recruiting sites and the patient commitment per clinical partner have been defined. Foundational plans have been established to support the proper implementation of the trial, including the trial management plan, data management plan, monitoring plan, and sample management plan. Ethical and regulatory approvals have been obtained for Austria, Israel, and Spain. The site in Israel has been activated, along with ten sites in Spain. In Austria, site activation visits have been scheduled.
Regulatory approvals for Ireland, Italy, France, and Germany are still pending due to discrepancies between national regulatory agencies. However, approval is expected at the beginning of the next reporting period, as all required documentation has already been submitted. During this reporting period, 76 samples have been analysed using HER2DX, and 61 patients have been randomised and enrolled in the trial.
Furthermore, the Statistical Analysis Plan and Data Management Plan have been finalised, outlining the procedures for analysing and managing the data. Two deliverables summarising current clinical guidelines have been submitted, along with a survey designed to gather input for the Health Technology Assessment (HTA) study. The Patient Advisory Board (PAB) has been established, including two representatives from each participating country. The PAB has reviewed patient information materials and provided valuable feedback. Additionally, methodologies to assess patient experience within the DEFINITIVE trial have been defined and delivered.
Regulatory approvals for Ireland, Italy, France, and Germany are still pending due to discrepancies between national regulatory agencies. However, approval is expected at the beginning of the next reporting period, as all required documentation has already been submitted. During this reporting period, 76 samples have been analysed using HER2DX, and 61 patients have been randomised and enrolled in the trial.
Furthermore, the Statistical Analysis Plan and Data Management Plan have been finalised, outlining the procedures for analysing and managing the data. Two deliverables summarising current clinical guidelines have been submitted, along with a survey designed to gather input for the Health Technology Assessment (HTA) study. The Patient Advisory Board (PAB) has been established, including two representatives from each participating country. The PAB has reviewed patient information materials and provided valuable feedback. Additionally, methodologies to assess patient experience within the DEFINITIVE trial have been defined and delivered.
At this stage the project, no results have been obtained yet.