We’re thrilled to have received funding of €4 million from Horizon 2020, the biggest research and innovation program in the European Union. Horizon 2020 believes that research is an investment, and is offering different companies and institutions almost €80 billion worth of grants from 2014 to 2020 – that’s in addition to the private investment that this money will attract. The program supports research projects in developing world-class science and innovation, making it easier for public and private sectors to work together. The aim is to enable more breakthroughs, discoveries, and world-firsts by taking great ideas from the lab to the market. Donated in June 2015, under grant agreement no 672570, our gift from Horizon 2020 is being used to fund a three-year project whose goal is to achieve final evidence for the clinical utility of MammaPrint. Our overall objective is to meet the reimbursement requirements in each targeted market and thereby gain comprehensive uptake by international clinical guideline committees and reimbursement bodies. As a result, many more breast cancer patients will potentially have access to the MammaPrint test. The MoTriColor study, part of the Horizon 2020 grant, is for the development of colon cancer subtypes. Further information can be viewed at motricolor.eu.
Our five specific project objectives are to 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)
- Additional clinical evidence on the predictive value (identify sub-populations of patients who are most likely to respond to a given therapy) of MammaPrint (work package 3 – STO high risk trial)
- 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)
- Clinical evidence on adherence to the results in breast cancer patients (work package 5 – PRospective study to measure the Impact of MammaPrint on adjuvant treatment [PRIMe])
- Required preconditions for full scale adoption in European and North American markets (work package 6 – communication and dissemination)
Our objectives will be achieved through four clinical trials and final commercialization preparations. These are organized into six work packages.
Work package 1 – project management
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-stage 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.
To 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.
To 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 data set revealed that there were not enough available to achieve this. NSABP could not fulfill its 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 the microarray technology on which the centralized MammaPrint test is based.
A comparable project, the STO high risk trial, was identified as being 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 by the West German Study Group (WSG) in Germany, between April 2015 and March 2016 in 27 centers with 452 patients.
Results were presented at SABCS in December 2016. Physicians’ 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 cases.1
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
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.
Published Results in Brief article (CORDIS website) (work package 6)
Study validates use of MammaPrint and BluePrint molecular diagnostics using targeted RNA Next Generation Sequencing (NGS) technology
Creation of new Agendia Center of Innovation and R&D Excellence
Publication of PRIMe study results in Breast Cancer Research and Treatment (work package 6)
Strong impact of MammaPrint and BluePrint on treatment decisions in luminal early breast cancer: results of the WSG-PRIMe study. R Wuerstlein, EM Grischke, O Gluz, R Kates, M Persoon, M Wasmayr, M Thill, S Hasmueller, M Knauer, R Pusch and N Harbeck on behalf of all WSG PRIMe investigators in Germany, Austria, Switzerland (2018) Breast Cancer Res Treat DOI: 10.1007/s10549-018-05075-x
MammaPrint recommended by National Comprehensive Cancer Network (NCCN) (work package 6)
STO high full project started (work package 3)
STO high pilot phase successfully completed (work package 3)
Completion of the PRIMe study (work package 5)
PRIMe trial results presented at St Gallen in Vienna (work package 5)
PRIMe trial results presented at 61st DGGG congress in Stuttgart (work package 5)
Collaboration with the Stockholm Breast Cancer Study Group initiated (work package 3)
Marketing plan finalized (work package 6)
Training of ABCSG Biobank employees completed (work package 2)
Data and communication management plans finalized (work package 6)
MammaPrint project launched
PRIMe trial started (work package 5)
— Horizon 2020 grant received
Where to next?
1. Wuerstlein R, et al. Results of multigene assay (MammaPrint®) and molecular subtyping (BluePrint®) substantially impact treatment decision making in early breast cancer: Final analysis of the WSG PRIMe Decision Impact Study. Poster presented at San Antonio Breast Cancer Symposium. December 2016; San Antonio, Texas.