In June 2015 Agendia received a grant of €4 million from the European Commission (EU)’s Horizon 2020 funding program.
The three year project was launched in July of that year and aims to provide additional evidence to further demonstrate the clinical utility of the MammaPrint 70-Gene Breast Cancer Risk-of-Recurrence Test to enable comprehensive uptake by international clinical guideline committees and reimbursement bodies. In doing so, even more patients with breast cancer across Europe will potentially have access to the MammaPrint test.

Objectives

The central aim of the project is to achieve the final evidence for the clinical utility of MammaPrint to meet the reimbursement requirements in each targeted market and therefore achieve comprehensive international adoption. This is supported by five specific project objectives:

  • Provide additional clinical evidence on the prognostic value (the likely course of breast cancer in an endocrine therapy-treated individual) of MammaPrint (Work Package 2 – ABCSG 8 trial)
  • Provide additional clinical evidence on the predictive value (identify subpopulations of patients who are most likely to respond to a given therapy) of MammaPrint (Work Package 3 – STO High Risk trial)
  • Provide additional clinical evidence on the clinical utility (the likelihood that the test will, by prompting an intervention, result in an improved health outcome) of MammaPrint (Work Package 3 – STO High Risk trial)
  • Provide the clinical evidence on the adherence to the results in breast cancer patients (Work Package 5 – PRospective study to measure the Impact of MammaPrint on adjuvant treatment (PRIMe))
  • Provide the needed preconditions for full scale adoption in the European and the North American market (Work Package 6 – Communication and Dissemination)

Project Summary – Work Packages

These objectives will be achieved through four clinical trials and final commercialization preparations which are organized within six Work Packages.

Work Package 1 – Project Management

Objectives: Due to the complex nature of the MammaPrint Horizon 2020 project and the associated data generated, project management is key to a successful delivery.

Work Package 2 – ABCSG 8 trial

The ABCSG 8 study was a randomized, controlled trial in postmenopausal women of ≤ 80 years with hormone receptor-positive early breast cancer performed by the Austrian Breast and Colorectal Cancer Study Group. The trial population was randomized after surgery to receive either five years of tamoxifen, or two years of tamoxifen followed by three years of anastrozole.This trial demonstrated the additional benefit of aromatase inhibitors over tamoxifen in postmenopausal women. Aromatase inhibitors are standard of care in postmenopausal breast cancer based on this trial.
Objectives: Demonstrate that MammaPrint is a prognostic indicator for predicting five and ten-year distant relapse-free survival in the retrospective-prospectively randomized estrogen receptor-positive postmenopausal ABCSG 8 breast cancer population.

Work Package 3 – STO High Risk trial

Between 1976 and 1990 the Stockholm Breast Cancer Study Group managed two randomized trials of postoperative radiation therapy vs. adjuvant chemotherapy among clinical high risk pre-and postmenopausal breast cancer patients. The postmenopausal patients were randomized between radiotherapy alone, radiotherapy in combination with tamoxifen, chemotherapy alone or chemotherapy in combination with tamoxifen. Long-term (20-year) follow-up of these patients is available.
Objectives: Determine the value of MammaPrint in predicting the benefit of chemotherapy on distant metastasis-free survival.
This Work Package was originally focused on the NSABP20 trial however detailed statistical analysis to determine the minimum number of patient samples required to reach significance on the dataset revealed that there were not enough available to achieve this. NSABP could not fulfill their commitment to provide sufficient samples for this project and as a result, the trial was replaced by the STO High Risk trial.

Work Package 4 – IBCSG 8 and 9

After the start of the MammaPrint project the IBCSG 8 and 9 study group recommended that genomic analysis of the patient samples be carried out using RNA-sequencing only, rather than using the microarray technology on which the centralized MammaPrint test is based.
A comparable project, the STO High Risk trial, was identified as able to provide the required clinical evidence on the effectiveness of MammaPrint to predict the need for chemotherapy, one of the priority objectives for full adoption of the test.

Work Package 5 – PRIMe

PRIMe is a prospective study evaluating the impact of MammaPrint and BluePrint on adjuvant clinical therapy decisions in hormone receptor-positive, HER2 negative breast cancer patients. The study was conducted in Germany between April 2015 and March 2016 in 27 centers with 452 patients by the West German Study Group (WSG).
The results were presented at SABCS in December 2016. Physician’s intended treatment changed in 28% of patients and adherence to the MammaPrint test result for chemotherapy decision-making was strong, with 90% for MammaPrint Low Risk and 93% for MammaPrint High Risk. After the test results, physicians’ confidence in their therapy decision increased in 33% of the cases.
Objectives: The objective of this study is to measure the impact of MammaPrint on adjuvant treatment decisions in hormone receptor-positive HER2-negative breast cancer patients.

Work Package 6 – Communication and Dissemination

Objectives: To inform a wide range of audiences about the project and its results including relevant stakeholders to increase market acceptance. To prepare for the uptake of MammaPrint in clinical practice guidelines and by reimbursement bodies.

Updates and Timeline

2017

July
MammaPrint recommended by ASCO Breast Cancer Guideline in focused update based on MINDACT trial data (Work Package 6)
June
MammaPrint recommended by the 2017 St. Gallen International Breast Cancer Guidelines in significant update (Work Package 6)
April
Completion of the PRIMe study (Work Package 5)
March
PRIMe trial results presented at St. Gallen in Vienna (Work Package 5)
German Gynecological Oncology Group (AGO) acknowledges MammaPrint in breast cancer guidelines as having Level 1A clinical evidence (Work Package 6)

2016

December
PRIMe trial results presented at 2016 San Antonio Breast Cancer Symposium (Work Package 5)
October
PRIMe trial results presented at 61st DGGG congress in Stuttgart (Work Package 5)
July
Collaboration with the Stockholm Breast Cancer Study Group initiated (Work Package 3)
February
Marketing plan finalized (Work Package 6)

2015

December
Training of ABCSG Biobank employees completed (Work Package 2)
August
Data and communication management plans finalized (Work Package 6)
July
MammaPrint project launched
June
PRIMe trial started (Work Package 5)
Horizon 2020 grant received

About Horizon 2020

The largest European Union Research and Innovation program to date, Horizon 2020 is providing almost €80 billion of funding over seven years from 2014 to 2020. The program facilitates public and private collaborations to support European companies and institutions in delivering world-class science, developing innovative technology and finding solutions to society’s challenges.