To create a genomic screening platform for advanced breast cancer and evaluate its efficacy in increasing the probability of a patient to be included in a clinical trial that is tailored to her specific molecular tumor type.
A GDPR and HIPAA compliant multimodal platform to store, manage, standardize and harmonize data generated from the different hospitals under a federated governance model.
Conclusion in numbers
This study represented the first step towards using data engineering solutions to advance our understanding of cancer biomarkers. Building upon the success of AGATA, SOLTI launched the HOPE study using Genomcore’s technology.
SOLTI is an academic research group that performs clinical trials of excellence in oncology. With a background of 77 clinical trials, they are positioned among reference oncology groups at a national and international level. Their mission is to promote innovative research that improves the well-being and prognosis of patients with breast cancer and other tumors. They strive to advance innovative research by supporting specialists in the development of translational clinical trials in oncology, especially in breast cancer. Their main activities involve academic, clinical and translational research, medical dissemination and scientific training programs with the aim of enhancing the talent of professionals and empower patients.
AGATA is a prospective, multicenter, pilot study conducted in 10 reference hospitals across Spain, including Arnau de Vilanova Hospital and University Clinical Hospital in Valencia; Clinic Hospital, Vall Hebron University Hospital, and Duran i Reynals Hospital (ICO) in Barcelona; Josep Trueta Hospital (ICO) in Girona; Son Espases University Hospital in Mallorca; Doce de Octubre University Hospital and Comprehensive Cancer Center CLARA CAMPAL (HM CIOCC) in Madrid; and Virgen del Rocio University Hospital in Sevilla. In the study, 260 patients (female and male) between 18-70 years with advanced or metastatic breast cancer were screened. Upon signed inform consent and confirmation of eligibility criteria – quality of life score according to ECOG scale ≤ 2 and a minimal life expectancy of 3 months among others – tumor samples were be obtained from the patients either by biopsy of metastatic cancer or from archived tissue previously available at the site, and their genomic profile was analyzed with an NGS panel of genes considered relevant to the tumor biology and treatment. Should any clinical trial match the patient’s molecular profile, she/he will be offered to participate in it and the available samples left after sequencing will be supplied when a central confirmation would be requested.
The study also counted with the economic support of grants by Novartis and Mutua Madrileña Foundation, and was largely financed by the Research, Development and Innovation National Plan and co-financed by the Carlos III Health Institute and the European Regional Development Fund (ERDF).
The identification of tumor drive genes and the development of targeted therapies have improved the outcome of some cancer types. However, the costs and complexity of implementing oncology precision strategies limit the access of this approach to just a minority of patients in the real clinical practice.
To date, conventional methods to select patients for clinical trials with anti-targeted agents according to molecular criteria are generally limited to the analysis of a few biomarkers. Several studies have shown how this strategy is inappropriate in case of infrequent molecular alterations and that the ideal strategy would consist in simultaneous examination of large numbers of actionable genomic alterations.
The AGATA study was designed as a proof-of-concept project to better characterize the genomic landscape of metastatic breast cancer and to facilitate patient access to matched-targeted clinical trials in Spain. The main objective was to create a network of hospitals throughout the country as a need to join efforts, set standards and optimize procedures for the benefit of all patients, so that the opportunity to participate in a genomic screening program can be offered to the great majority of hospitals that lack the technology required for these tests. So that patients diagnosed with this type of tumor had access to a personalized therapy according to the molecular profile of their tumor, most of them through clinical studies.
Carrying out a pioneering multi-center clinical study entails challenges on several levels. Hospitals use different customized sequencing gene panels requiring bioinformatics support and strategies to unify, standardize and facilitate data analysis. Moreover, results from tumoral DNA sequencing were evaluated by a molecular advisory tumor board (MTB) comprised of medical oncologists, pathologists, and molecular biologists who required controlled access to data, which needed to be harmonized across all datasets and cohorts to ensure reproducibility. Correlative analysis of tumors and liquid biopsis was performed to look for clinically-predictive biomarkers and mechanisms of resistance.
Genomcore and SOLTI joint forces to “create a high-potential research tool to help address scientific/clinical concerns and expand our knowledge of biology and treating breast cancer,” explained Dr Aleix Prat, coordinator of the Solti Scientific Committee.
Genomcore provided its multimodal platform especially designed for managing collaborative projects. The platform offers a GDPR and HIPAA-compliant framework for the store, management, standardization and integration of all kinds of data and analytic processes. This centralized data storage and analysis environment in the cloud is accessible from anywhere and can be adapted to the unique needs of each project so that participants can share data, metadata, analysis tools, and results, facilitating seamless collaboration and unlocking the full potential of research data.
Genomcore’s platform provides an intrinsic metadata system to ensure data is properly organized and structured. Customized data models are defined for each type of data, such as clinical and personal data, genomic data or the details of a laboratory experiment. Therefore, Genomcore can ensure that data is standardized and harmonized, which facilitates efficient analysis and interpretation of the data. By ensuring that all data is collected, processed, and analyzed in a consistent manner, researchers can more easily compare and contrast different data sets, identify patterns and correlations, and draw meaningful conclusions from the data.
The pseudo-anonymized data –being primary data and data resulting from the project analyses– is stored in the platform and is made accessible only to project partners via controlled user access. The Genomcore platform provides a flexible database model to ensure segregation of information blocks -interoperable data structures- that allow defining granular permissions on different levels of data access avoiding unforeseen usage or disclosure to non-authorized partners.
In addition, our platform ensures standardized data production with version-controlled analyses and pipelines. Hospitals have different bioinformatic pipelines for many reasons, such as different types of sequencing platforms, clinical and research needs, or availability of in-house computation resources. Despite the variation in bioinformatic pipelines used, it is important to ensure that the pipelines used are validated and produce reliable and reproducible results. This can be achieved with the Genomcore solution as each bioinformatic pipeline was encapsulated so every hospital could analyze the data with their specific pipeline or a generic one provided to the whole consortia, so results were automatically standardized.
CONCLUSIONS IN NUMBERS
Genomcore multimodal platform served as a data repository to store, manage, standardize and integrate data generated from the different hospitals and laboratories that formed the AGATA study network. Moreover, data was made accessible to the different professionals including medical oncologists, pathologist and data analysts among others, via our controlled access. Genomcore can provide the necessary technological framework to enable a cost-effective federated approach for transferring information between the clinic and research, with the ultimate goal of advancing personalized medicine and biomedical research.
The AGATA study allowed the identification of a known mutation in 63% of the patients and 11% of them could benefit from a targeted treatment based on the molecular study of their tumor. These results, published in the journal Frontiers in Oncology, will contribute to designing personalized medicine protocols for this type of cancer.
Additionally, Genomcore became the chosen technology for multimodal data repositories for other prospective clinical trials in SOLTI.
At Genomcore we are very proud to have been part of the AGATA study by providing our innovative multimodal unified datastore. This study demonstrates that when scientific and clinical collaborative technology exists it is possible to run a multi-center molecular screening program in a real-world setting.
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