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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 3 - MammaPrint (Improved breast cancer care by innovative diagnostic test MammaPrint)

Teaser

Summary

Agendia NV, a Dutch SME founded in 2003 as spin-off from the Netherlands Cancer Institute, is a commercial-stage molecular diagnostic company.
Agendia focusses on the discovery, development and commercialization of innovative products to improve the quality of life for cancer patients by providing healthcare professionals with critical information to enable safe and effective personalized treatment.

Breast cancer treatment decisions made by physicians have traditionally relied on clinicalpathological factors such as hormone receptor status, age, tumor size, tumor grade and lymph node involvement. Based on these criteria clinical guidelines recommend adjuvant therapy for all patients with early invasive breast cancer. However, this \'one size fits all approach\' leads to a proportion of patients being over- or under-treated as the risk of recurrence is difficult to determine.

The advancements in molecular diagnostics are starting to improve the prognosis and treatment of breast- and other cancers, and specifically gene expression assays aid in designing a personalized treatment plan.
One of the products Agendia is developing is MammaPrint, an assay that identifies the risk of recurrence of breast cancer by looking at the patientsâ€™ specific tumor characteristics. The test measures the expression profile of 70 genes that play a role in metastasis of the tumor.
MammaPrint can be used for all early stage breast cancer patients and stratifies patients in two distinct groups, â€œLow Riskâ€ and â€œHigh Riskâ€ of cancer recurrence within 10 years. By providing this risk classification, MammaPrint aids in identifying which breast cancer patients will gain the most benefit of adjuvant chemotherapy.

The objective of this project is to achieve the final convincing evidence for the clinical utility of MammaPrint and to reach worldwide full-scale adoption of the assay.
To accomplish this goal there are three major focus points:
1. Inclusion of MammaPrint in the influential clinical guidelines
2. Adoption of MammaPrint in reimbursement schemes
3. Acceptance of MammaPrint by clinicians

These objectives have been translated into four clinical trials, one prospective study and three retrospective studies, each of which specifically has been selected to accomplish one or more of the above objectives.
The use of molecular diagnostic tests to stratify breast cancer patients by risk of recurrence has the potential to eliminate the utilization of unnecessary or insufficient chemotherapy.
As is generally known, chemotherapy often cause physical and psychological problems that affect the patientâ€™s quality of life. If, by using MammaPrint, overtreatment can be decreased, the quality of life of breast cancer patients will be increased significantly. Moreover, avoidance of overtreatment also will significantly reduce healthcare costs (i.e. less use of medication and less adverse effects to be treated).

Work performed

The first year of the current project focussed on the start-up of the clinical trials and the different activities related to the three objectives.

In Germany a prospective study on the impact of MammaPrint on adjuvant treatment decisions in hormone receptor positive and HER2 negative breast cancer patients, the PRIMe study, was successfully implemented.
The inclusion rate of patients into the trial was higher than expected and enrollment of all 450 patients was therefore completed ahead of schedule in March 2016.
The initial results of the PRIMe study show a high degree of adherence to the test and clinicians indicated the MammaPrint result has impacted their treatment decisions.
The acceptance of MammaPrint by German clinicians as a diagnostic tool that contributes to the improved selection of patients that need adjuvant chemotherapy, will ultimately lead to reduced application of chemotherapy and have an impact on healthcare costs.
A marketing strategy is currently being developed to stay in contact with the German hospitals that participated in the PRIMe study to ensure uninterrupted availability of the MammaPrint test for their breast cancer patients.
The first overview of the PRIMe study has already been presented on the German Senology congress, and arrangements are being made to further communicate and publish the results of the study.
The next step is dissemination of the positive results in Germany and focusing on adoption of the MammaPrint test into the German healthcare reimbursement system. Activities have been employed to contact institutes that are responsible for reimbursement in Germany.

One of the retrospective studies in this project uses breast tumor samples from the ABCSG 8 study and is currently active. The protocol for this study has been written and approved by the ethical committee of the Medical University of Vienna.
As the tumor samples are stored and prepared for MammaPrint analysis in Vienna, Agendia has conducted a training and validation program for the ABCSG Biobank laboratory to accomplish a consistent and quality controlled tissue processing procedure.The validation was successful and a start was made with the first set of study samples and the analysis of the MammaPrint results.

Final results

The acceptance of MammaPrint by clinicians and the positive results on adherence to the MammaPrint test results are a good starting point to further strengthen Agendiaâ€™s position in the market and to become one of the a key players in the field of gene expression profiling.
The results will especially be crucial for the quality of life of all breast cancer patients as overtreatment with chemotherapy can be avoided in a substantial number of patients. As a consequence the healthcare costs can be reduced.

In April 2016 the results of a large international clinical study have been presented, the MINDACT trial (Microarray In Node negative (or 1-3 LN+) Disease may Avoid ChemoTherapy).
The study investigated the clinical utility of MammaPrint to select patients for chemotherapy treatment and the outcome after 5 years follow-up has been presented: patients with a MammaPrint Low Risk profile turn out to have such a good prognosis that adjuvant chemotherapy does not provide any benefit. The recommendation derived from these results is to apply MammaPrint to the tumors of all patients with a suspected high clinical risk of recurrence.
The manuscript with the results of the MINDACT study has been accepted for publication in the New England Journal of Medicine.
Agendia is preparing presentations and is contacting KOLâ€™s in Europe and health insurance companies to bring the MINDACT results to their attention.

In the Netherlands an update of the clinical guidelines with regards to treatment of breast cancer is expected by the end of this year. The results of the MINDACT trial will be incorporated in this guideline. Furthermore, efforts are put into implementing MammaPrint into the Dutch standard health insurance.