FOCU.SE is a new Swedish study in which genetic analysis of tumours is used to match cancer patients with targeted drugs outside of approved indication. The aim is to give more people access to effective treatment, while gathering valuable knowledge for the future.

In the national clinical study FOCU.SE, approved drugs will be tested on new patient groups with advanced cancer where treatment options have been exhausted. By analysing the genetic profile of the tumours, patients can be matched with targeted therapy. Even before the study has begun, four targeted drugs have been secured. More drugs will be included as the study progresses. As part of the Swedish government’s investment in precision health, the study is being funded with SEK 44 million.

“We are delighted with the support from the government which enables us to now launch the FOCU.SE study. With the FOCU.SE study, we can provide targeted treatments in a structured way to patient groups where it is otherwise difficult to conduct large drug studies, such as pancreatic cancer, bile duct cancer and sarcoma,” says Edvard Abel, medical director at the Clinical Trial Unit Oncology Sahlgrenska University Hospital and responsible for the study.

Digital collaboration on treatment decisions

A central part of the study is the so-called molecular tumour boards, where the results of the analyses are discussed to determine whether any of the study’s treatments may be suitable for the patient. The Molecular Tumor Board Portal (MTBP) tool – a digital platform and clinical decision support system for test results and data – will be used as support. With the help of this tool, doctors from different hospitals can participate in national conferences and discuss treatment options in real time.

The technical solution was first tested within the European research collaboration Cancer Core Europe and is now being adapted for national use in Sweden.

Patient council contributed to study protocol

Early on in the development of FOCU.SE, a patient council was formed, which has been active in developing study protocols and consent forms.

“We have shown how important it is for patients to be involved early on in the design of studies. Our commitment has also made it easier to include patients in the study”, says Margareta Haag, patient representative and chair of the Network Against Cancer:

Edvard Abel agrees:

“Working with the patient council has been time well spent and a great benefit to the entire project.”

Valuable knowledge for future treatment decisions

FOCU.SE makes it possible to systematically follow up on treatments outside of approved indications. This generates new knowledge about the effects and side effects of treatments – knowledge that can form the basis for future approvals and better treatment decisions.

In addition, FOCU.SE serves as a national platform for molecular testing, enabling patients to be identified more quickly for participation in other studies.

“The established collaborations for data sharing with similar studies provide entirely new opportunities to quickly answer research questions that are difficult to address in a single country. The ability to continuously add new drugs is also built into the study design. The broad genomic profiling that is carried out can both support clinical decisions and help identify patients for other studies. In this way, FOCU.SE, in collaboration with industry and international initiatives, can become a key to more clinical trials in Sweden,” says Anders Edsjö, senior physician in pathology at Region Skåne and deputy director of GMS.

About FOCU.SE

• FOCU.SE has been developed within the framework of the Testbed Sweden Precision Health Cancer project, with funding from Vinnova and Swelife.
• The project is backed by a broad consortium of stakeholders, including Genomic Medicine Sweden (GMS), SciLifeLab, university hospitals, the Swedish Institute for Health Medical Economics, the Stockholm School of Economics, industry partners and patient organisations.
• FOCU.SE is being conducted at all university hospitals in Sweden, which means that patients from across the country can participate.
• The study is a continuation of the work in the previous regional study MEGALiT and is being conducted in collaboration with several European countries within the EU projects PCM4EU and PRIME-ROSE, with focus on drug repurposing, i.e. evaluating existing drugs for new cancer indications.
• The first four targeted drugs in the FOCU.SE study are Olaparib, Amivantamab, Tepotinib and Ivosidenib, all secured through collaboration within PRIME-ROSE.

The Swedish government announces that it will fund Genomic Medicine Sweden (GMS) with SEK 80 million in 2025. The money will go to continued efforts to develop and sustainably implement precision medicine in healthcare in the areas of cancer, rare diseases and microbiology.

“We are grateful for the Ministry of Social Affairs’ increased support and long-term investment in GMS. This work that we do together, healthcare, academia, patient organisations and industry, is an important part of the continued development towards precision health for all patients,” says Mats Ulfendahl, Research Director Region Östergötland and chairman of the GMS Steering Committee.

The funding will be used for continued investments in the areas of childhood cancer, rare diseases, acute leukaemia, solid tumors and microbiology to further develop precision diagnostics, and continue implementation and scale up use in healthcare.

Precision medicine database for childhood cancer

The work of GMS Childhood cancer has led to the implementation of whole genome sequencing in routine care for all children diagnosed with cancer in Sweden. To further advance the development of personalised treatment for children with cancer, the large data sources that already exist need to be linked together. In collaboration with the Swedish Childhood Cancer Fund, the National Genomics Platform the Child Tumour Biobank and the Swedish Childhood Cancer Registry, among others, a system is being built to link large-scale data types such as whole genome sequencing, use of targeted therapy, survival data and digital imaging in a systematic way.

• SEK 4.9 million will be used to continue work on the BrainChild innovation project.

Long-read sequencing to solve complex rare diseases

Whole genome sequencing of individuals with suspected rare diseases enables diagnosis for nearly 40 percent of previously undiagnosed patients. For patients with complex chromosomal abnormalities, current standard methods in routine care have been insufficient and GMS Rare diseases has shown that long-read sequencing has great potential for this patient group.

• SEK 14.5 million may be used for a national implementation project of whole genome sequencing for rare health conditions based on long DNA reads, and for continued national/international work on children with undiagnosed rare health conditions with malformations and/or intellectual disabilities.

Precision diagnostics for acute leukaemias

Several different genetic analyses are currently used to diagnose acute leukaemia within healthcare. Pilot projects carried out within the GMS show that whole genome sequencing as a single method is likely to replace current analyses. In addition, it can provide new and important information in a significant proportion of cases, which can improve both risk assessment and treatment decisions.

• SEK 6.3 million is allocated to the fcontinued work on national implementation of whole genome and transcriptome sequencing for adults with acute leukaemia and for the development of gene panel analysis for sensitive detection of residual disease.

Scale-up and further development of precision diagnostics for solid tumours

The GMS-developed broad gene panel covering more than 500 cancer-linked genes has since 2022 been gradually implemented in healthcare to provide detailed molecular information that can lead to targeted treatment, the possibility for patients to be included in clinical studies and to improved diagnostics and prognostics. In addition to scaling up and further developing the analysis of tumour tissue, analyses of circulating tumour cells in blood, known as liquid biopsies, are being developed, which provide increased opportunities for diagnosis, follow-up and, by extension, early detection of disease.

• SEK 19.5 million will be used for scaled-up implementation and further development of precision diagnostics (tissue and liquid biopsies) for solid tumours in routine care and for clinical studies.

Limiting the spread of antibiotic-resistant bacteria

In the field of microbiology and infectious diseases, GMS has established a national collaboration between all clinical microbiological laboratories, SciLifeLab Clinical Genomics and the Public Health Agency of Sweden, where, by developing and using various precision diagnostic methods and shared analysis tools for interpreting data, work is being done to detect and limit the spread of resistant bacteria across the country. Real-time data sharing via the National Genomics Platform will be key to this.

• SEK 4.8 million is allocated for continued work on implementing precision diagnostics in infectious diseases, including the detection of antibiotic resistance, and for increased data sharing between regions for the detection of outbreaks of antibiotic-resistant bacteria.

In most of the funded projects, the Clinical Genomics platform at SciLifeLab will be an important infrastructure and collaborative partner for developing new precision diagnostic solutions and bioinformatic analysis tools.

SEK 30 million is also allocated to GMS to continue to strengthen the national work and ensure long-term sustainable development that promotes equal implementation of precision health in the country. The funding will also enable GMS to continue developing the National Genomics Platform so that data can be made available nationally and internationally.

“This investment gives us the opportunity to continue our hard work to develop and introduce precision medicine in a sustainable way in healthcare so that patients have equal access wherever they live in the country. This is a true team effort, both between all of us hundreds of clinicians and diagnosticians working within GMS, but also with the many other actors in Sweden we collaborate with,” says Richard Rosenquist Brandell, Director of GMS.

Image: Jessica Stegrud, Social Policy Spokesperson for the Sweden Democrats, and Minister for Health Acko Ankarberg Johansson at a press conference on the support for Genomic Medicine Sweden. Photo: Mikaela Friedman.

Today, the Swedish Ministry of Social Affairs announces that it is granting SEK 49.5 million to Genomic Medicine Sweden (GMS) to develop and intensify work in precision diagnostics, childhood cancer, rare diseases and data sharing.

“This extensive investment from the government gives GMS the opportunity to continue its work to ensure that more individuals have access to precision diagnostics and personalized care, treatment and follow-up. The pilot projects are also very important for an equal implementation of precision medicine in Sweden and a joint learning. Moreover, we will have the opportunity to implement precision diagnostics for clinical studies. This is an important piece of the puzzle in Sweden’s efforts and ambition to be an international leader in the transition to precision medicine,” says Richard Rosenquist Brandell, Director of GMS.

The funding will go to four targeted initiatives: a national pilot in precision medicine for children with rare syndromes (SEK 15 million), a pilot on precision diagnostics for clinical studies in cancer (SEK 10 million), the establishment of a precision medicine database in pediatric cancer (SEK 10 million), and increasing opportunities for national and international data sharing of genomics data (SEK 14.5 million).

“Today, not all children with rare disease of birth defects and/or intellectual disabilities are offered whole genome sequencing for refined diagnostics. The continued support from the Ministry of Social Affairs gives us a great opportunity to both provide children with rare syndromes with a diagnosis, to build expertise nationally and participate in international collaborations to provide even more individuals with a diagnosis. This is crucial for care, treatment and support from society and contributes to a better quality of life,” says Ann Nordgren, Professor and Chief Physician at Karolinska University Hospital.

“Sweden is already a leader in collecting data from children with cancer. Today, this information is spread across different databases. This initiative is a first step towards linking large-scale data types such as whole genome sequencing, use of targeted treatments, survival data and digital imaging in a systematic way. We will work in partnership with the Swedish Childhood Cancer Fund, the National Genomics Platform, the Swedish Childhood Tumor Biobank and the Swedish Childhood Cancer Registry for a system that makes it possible to follow the development of precision medicine in the field of childhood cancer while paving the way for future AI applications,” says David Gisselsson Nord, co-chair of GMS Childhood cancer, professor at Lund University and Chief Physician at Region Skåne.

Read press release from Ministry of Social Affairs (in Swedish).
Read press release from Swedish Childhood Cancer Fund (in Swedish): Regeringen finansierar BrainChild med 10 miljoner kronor.

Photo: Acko Ankarberg Johansson, Minister for Health, and Ola Mattsson, Secretary General of the Swedish Childhood Cancer Fund, present the investment. 

A population-based study of 6,000 lung cancer patients shows that patients with the KRAS G12C mutation have a high risk of brain metastases. Surprisingly this is not linked to worse survival. The study was conducted by researchers affiliated with Genomic Medicine Sweden and the National Swedish Lung Cancer Registry with support from Amgen.

Each year, approximately 4,000 patients are diagnosed with lung cancer in Sweden. In the most common form, non-small cell lung cancer (NSCLC), the tumor development is propelled by changes in genes that control cell proliferation, so called “driver genes”. The most commonly affected gene is KRAS, where several different gene mutations, for unknown reason, result in a very heterogeneous group of tumors. One of these KRAS mutations, the G12C variant, has been in focus in recent years because it can be targeted by specific drugs.

The study includes more than 6,000 patients in the Swedish National Lung Cancer Registry where a gene sequencing analysis was performed at diagnosis. The results show that the KRAS G12C mutation is strongly linked to smoking, more common in female patients and affects the spread of the cancer in a unique way compared to other KRAS mutations.

Johan Botling. Photo: Johan Wingborg.

“The most interesting finding is that lung cancer patients with the G12C mutation in KRAS are more likely to get brain metastases than patients with other mutations,” says Johan Botling, Senior consultant at Sahlgrenska University Hospital and professor of pathology at Gothenburg University, who led the study.

However, the survival analysis showed that patients with the KRAS G12C mutation who presented with brain metastases at diagnosis did not have a worse outcome compared to patients with other patterns of metastatic tumor dissemination.

“This finding surprised us. We noted that these lung cancer patients seem to get brain metastases earlier in their disease than others, but at the same time have fewer metastases in other organs. This might explain why these patients do better then expected,” says Johan Botling. In further studies, we will investigate how different KRAS mutations affect the response to treatment with chemotherapy, immunotherapy and targeted drugs.

An essential precondition of the study is that results from mutation diagnostics with NGS (next-generation sequencing) have been reported at a national level for lung cancer patients to the National Lung Cancer Registry since 2015.

Gunnar Wagenius. Photo: Johan Linberg, Karolinska University Hospital.

“The National Lung Cancer Registry is a unique resource for research where we, in order to evaluate existing treatments and develop new therapeutic procedures, can link molecular data with other patient information such as age, gender and treatment outcome. This is the first study where we have linked mutation data from the tumors with patient data in the registry,” says Gunnar Wagenius, Associate Professor and Senior consultant oncologist at Karolinska University Hospital and registry holder of the National Lung Cancer Registry.

“Thanks to early adoption of diagnostic biomarker testing in Sweden, we have the opportunity to generate high-quality real-world-data on large patient populations. This is of utmost importance for the design of new clinical trials in the area of targeted treatment. For us at Amgen, working with GMS and the lung cancer registry has been a rewarding collaboration that has resulted in important knowledge with global impact beyond Sweden,” says Sandra Eketorp Sylvan, Medical Director of Amgen Sweden.

“In this project we looked at mutations in one gene and obtained interesting results. With even broader gene sequencing developed within the GMS network, it will possible to explore the impact of hundreds of genes on large national patient populations. This knowledge will help us to better understand different types of lung cancer and how to improve treatment for individual patients,” concludes Johan Botling.

Publication
KRAS G12C Mutant Non–Small Cell Lung Cancer Linked to Female Sex and High Risk of CNS Metastasis: Population-based Demographics and Survival Data from the National Swedish Lung Cancer Registry Isaksson J, Berglund A, Louie K, Willén L, Hamidian A, Edsjö A, Enlund F, Planck M, Vikström A, Johansson M, Hallqvist A, Wagenius G, Botling J. Clin Lung Cancer. 2023 Sep;24(6):507-518. doi: 10.1016/j.cllc.2023.05.002.

Photo: iStock

Genomic Medicine Sweden and the Danish National Genome Center has signed an agreement with the aim to advance genomics and precision medicine and its implementation in healthcare. The joint partnership will focus on the development and implementation of innovative solutions and models to provide genomic-based precision medicine at a national level.

“Denmark and Sweden have many similarities in our respective healthcare systems, but also differences to learn from. The Danish National Genome Center, the Danish equivalent to Genomic Medicine Sweden will be an important partner in developing and exchanging experience and expertise on how to continue advance and implement precision medicine for the benefit of our patients and societies”, says Richard Rosenquist Brandell, Director for Genomic Medicine Sweden.

And Bettina Lundgren, CEO of the Danish National Genome Center continues:
”We look very much forward to share experiences with our Swedish neighbors. The MoU will facilitate further collaborative activities to help tackle some of our common challenges in implementing personalized medicine, such as within standardization as well as storage of and access to genomic data. Working together will ensure that patients receive the best treatment possible”.

In this strategic partnership, the Danish National Genome Center and Genomic Medicine Sweden will share experience of the implementation of genomics and precision medicine approaches in healthcare and mutually demonstrate the clinical utility of genomic medicine for different diseases. This partnership will promote faster and more successful advances by building common approaches for implementation of precision diagnostics and precision medicine in healthcare. This includes solutions and models for data processing and sharing, ethical issues and health economy.

The Memorandum of Understanding (MoU) was signed by Bettina Lundgren and Richard Rosenquist Brandell during the Nordic Precision Medicine Forum in Stockholm on April 28th where they took part to discuss the future developments of precision medicine.

Bettina Lundgren and Richard Rosenquist Brandell. Photo: Lene Cividanes

The Swedish national infrastructure Genomic Medicine Sweden (GMS) will receive an additional SEK 220 million investment. The investment will facilitate the continued introduction of precision medicine into Swedish healthcare, so that every individual in Sweden has access to more precise diagnostics and personalised care.

Mats Ulfendahl. Photo: Region Östergötland

The Swedish government is allocating an additional SEK 96 million via Sweden´s innovation agency Vinnova, an investment matched by SEK 124 million in co-financing from regional health authorities and universities.

“This is highly gratifying news from the Swedish government and Vinnova. We welcome this funding for GMS over the coming three years. At the same time, we are in dialogue with the Swedish regions and the Government Offices of Sweden regarding a long-term funding and governance model, something that is a necessity if precision medicine is to be truly put into action,” says Mats Ulfendahl, Chair of the GMS Steering Committee and Research Director at Region Östergötland.

Collaboration is key to success

Since its launch in 2018, GMS has built up a national organisation based on collaboration between healthcare, academia, industry, patient organisations and public authorities. Support within healthcare is a key issue if new diagnostic tools are to be introduced into healthcare and contribute to more personalised care and treatment, i.e., precision medicine.

The seven regional Genomic Medicine Centres established at Sweden´s university hospitals are the engine for introducing precision medicine into healthcare. This process is supported by a national genomics platform that will make it possible to store, analyse and share the enormous volumes of data generated in a harmonised and secure manner, thus making the knowledge more accessible. The SciLifeLab Clinical Genomics platform is also a central part of the technical development of new diagnostic tools.

Closer links to clinical studies

In a national collaboration, a new diagnostic toolkit for detecting genetic variations has been developed for use in healthcare nationwide. This includes broad gene panels and whole-genome sequencing for analysing cancers and rare diseases, which will contribute to improving the diagnosis, treatment and follow-up of patients. During the next phase of GMS, work will also focus on linking these refined genetic diagnostics to clinical studies, so that more patients have access to the increasing number of new, targeted therapies.

Maria Montefusco. Photo: Joakim KE Johansson

“As GMS’ infrastructure, expertise and capacity is implemented nationwide, correct diagnosis and treatment will be made available more promptly to more patients. This will make it easier to provide equitable care, even for persons with the rarest diseases and irrespective of where in the country one lives. This is not the case today,” says Maria Montefusco, Chair of Rare Diseases Sweden, the Swedish association of rare-disease patient organisations.

“The patient and next of kin perspective is a crucial part of GMS’ future development. The organisation is founded on real clinical and social needs for diagnosis and treatment. Our collaboration is off to a good start and we are looking forward to even greater involvement in the work of, for example, achieving data sharing and access to clinical studies,” continues Maria Montefusco.

An organisation with long-term sustainability

One important step towards ensuring that the introduction of precision medicine in healthcare is sustainable in the long term and does not lose momentum compared to the rest of the world is to establish GMS as a long-term, sustainable organisation. This issue is addressed in the government’s Research and Innovation Bill, which sees GMS as a “load-bearing function” if Sweden is to pioneer the implementation of precision medicine in healthcare services. The Swedish Agency for Health and Care Services Analysis also made the same point in a report published earlier this year.

Frida Lundmark. Photo: Lif

“GMS has accomplished a great deal during its first four years; now, together and in close collaboration, it is our responsibility to accelerate the introduction of precision medicine. The Partnership Group for Health and Life Sciences is currently preparing a roadmap for precision medicine in which one fundamental area is models for how central government and regional health authorities can collaborate on complex issues,” says Frida Lundmark, convener of the Partnership Group’s working group on precision medicine/ATMP and policy advisor to Lif, the trade association for the research-based pharmaceutical industry in Sweden.

Vinnova is co-financing the investment with an additional SEK 96 million to GMS for the period 2021–2024. Sweden’s seven regional health authorities with university hospitals and seven universities with medical faculties will be contributing SEK 124 million. This funding is intended to contribute to the ongoing introduction of precision medicine into healthcare, strengthening Swedish research and promoting new research and innovation collaborations between industry, healthcare and academia.

Darja Isaksson. Photo: Vinnova

“Genomic Medicine Sweden has built up an impressive network and IT infrastructure that is crucial to the development of precision medicine in Sweden and reinforces our position as an innovative country. Our intention with this investment is to contribute to continued collaboration that makes healthcare more preventive, accurate and equitable,” says Vinnova’s Director General Darja Isaksson.

Photo: iStockphoto