The PCM4EU project was launched in January 2023 and will be running over two years. The project is coordinated from Leiden University Medical Centre (LUMC) and has altogether seventeen partners from fifteen European countries.
Cancer is one of the leading causes of death and morbidity in the EU with 3.7 million new cases every year. The PCM4EU consortium shares the ambition of Flagship No. 6 of the EU Beating Cancer Plan, the “Cancer Diagnostic and Treatment for All” initiative to increase knowledge and access to innovative cancer diagnosis and treatments to improve quality of life and survival for cancer patients.
Numerous medicines targeting specific molecular alterations have reached the market over the last two decades. However, there is unequal access to these drugs within and between the EU countries due to several challenges that include access to adequate diagnostics to identify patients that can potentially benefit from these targeted drugs, knowledge / education gaps, reimbursement hurdles and limited access to PCM clinical trials.
The PCM4EU consortium has a track record on implementation of molecular diagnostics coupled with academically led drug repurposing PCM trials across borders in countries in North-western Europe. The underlying concept for PCM4EU is therefore to scale-up the already successful DRUP-Nordic alliance network within PCM, maintaining its original grass-root spirit, bottom-up initiatives while at the same time addressing identified areas of common need as well as supporting new partners as effectively as possible.
As PCM is based on targeting driver mutations in the tumour, adequate next-generation sequencing-based molecular diagnostics and clinical decision support systems are crucial.
The PCM4EU consortium will evaluate current standards and provide best practice guidelines and recommendations on state-of-the-art genomics diagnostics, implementation and interpretation. Moreover, through harmonisation and collaboration, the consortium will facilitate mechanisms for interpretation of molecular and clinical data, thereby anticipating the benefits of the upcoming European Health Data Space. Cross-border access to PCM is one of the focus points of this consortium. Cohorts of patients with rare mutations / tumour types can be filled simultaneously in multiple countries to obtain faster answers. Finally, facilitating implementation of the results into the healthcare system in a cost-effective way for future patients and providing education for all stakeholders, including physicians, pathologists, patients and decision makers, are crucial aspects that will be taken forward.
PCM4EU consists of six closely aligned and fully integrated work packages. Among these, WP1 is responsible for the overall project coordination. The other work packages are described in more detail below.
There is a clear need for increased knowledge and standardization of next-generation sequencing (NGS)-based tests directed at access to targeted cancer therapy. NGS platforms and gene panels differ in types of sequencing errors they are prone to, data tools need determination and cut-offs and have curation steps that need to be defined. Furthermore, interpretation and decision tools depend on different algorithms and databases.
This work package aims to increase knowledge and standardization of NGS-based tests and clinical decision support systems (CDSS) accessible for precision cancer medicine. Within the PCM4EU consortium, more than 63 000 NGS-based gene panels and more than 12 000 whole-genome sequencing analysis have already been performed. Furthermore, more than 15 000 cancer patients have been discussed at Molecular Tumor Boards (MTBs). Taking advantage of this large-scale and constantly growing dataset as a reference, work package two will provide guidelines and recommendations for next-generation centers setting up NGS-based tests and MTBs.
Furthermore, taking into account the need for synchronization of various CDSS tools currently used across Europe, the aim is to improve the knowledge and implement a standardized way of working.
The DRUP-like studies are phase II combined umbrella-basket trials where patients with advanced cancers receive targeted therapies matched to genomic alterations in their tumour. Currently, such trials are running in the Netherlands, in the Scandinavian countries as well as in France, all using similar protocols and study endpoints.
Work package three focuses on precision oncology and on how to expand the family of DRUP-like clinical trials to more European countries. A buddy-concept where established trials team up with upcoming trials will secure an efficient knowledge transfer for the purpose of implementation of next-generation trials across Europe.
Furthermore, work package three will focus on establishing effective ways of data sharing, including building a data aggregation platform.
There is an increasing discrepancy between what cancer patients, society and diverse commercial entities (e.g. digital healthcare solutions, pharmaceutical industry, biotech and diagnostics) expect, and what the healthcare system delivers regarding access to molecular diagnostics and targeted therapy all over Europe. Precision cancer medicine has proven to be difficult to implement for countries with public healthcare systems. In general, there is a lack of knowledge about the social impact of PCM implementation, of detailed guidelines on the appropriate clinical decision-making process to follow according to up-to-date evidence and of budget impact considerations. We believe that one key aspect for addressing these challenges is to harmonize country-specific, bottom-up initiatives with national strategies and financing options. This requires clear recommendations for the use of molecular diagnostics and associated anti-cancer treatments across the different tumour groups that are well anchored in the oncological community.
Work package 4 will therefore facilitate development of national guidelines and recommendations for who and what to test by next-generation sequencing and how to act on data. This will be done in close cooperation with ESMO guidelines. Sustainable use of available healthcare resources for implementing PCM is important for all participating countries. WP4 will therefore focus on the added value of using advanced diagnostic tests, showcase the cost-effectiveness of a few PCM treatment cohorts, the cost of implementation and on the value of the novel implementation. The work will balance general challenges with implementing PCM, with country specific challenges.
Moreover, to facilitate a patient-centric implementation and communication, information about ongoing and planned PCM initiatives in Europe, molecular diagnostics and its added value will be provided throughout and after the project period.
For cancer patients with good performance status who have exhausted all available treatment options or for whose cancer no effective standard of care exists, clinical trials are an important way to access treatment. Ideally, all eligible patients in a given country should have equal access to clinical trials, including to the trials of the DRUP family, independent of geographic location or socio-economic circumstances.
For all eligible patients to be able to participate in a DRUP-like trial in their country of residence, national infrastructures and processes are needed. Ideally, a country should have several participating centres to ensure access close to a patient’s location and referral systems to ensure equitable, high-quality care. However, having at least one single national centre with access for all patients from the country ensures that patients can be treated within their own national healthcare system.
Failing that, cross-border access to clinical trials remains an important access road for patients but remains problematic. The EU Directive on cross-border healthcare clarifies patients' rights to access safe and good quality treatment across EU borders with reimbursement by their home country. However, the directive is primarily based on standard of care and highly specialized treatment, and does not account for cancer patients seeking access to clinical trials abroad.
PCM4EU is in this work package therefore focusing on how to ensure cross-border and equitable access to precision cancer medicine clinical trials by facilitating broad cooperation and innovative initiatives between the relevant actors (e.g., healthcare providers, regulators) of different Member States at national, regional and local level. In particular, work package 5 will organise a crowd-sourcing event on cross-border access to clinical trials in collaboration with the European Cancer Patient Advocacy Community to create an open resource. Furthermore, the team will document and analyse the past implementation of DRUP-trials, to be able to give recommendations on how to successfully implement PCM trials that are equitable and work cross-border.
Access to precision cancer medicine varies significantly in the different EU countries, depending on the national healthcare systems. As a consequence, the principles of molecular medicine are not consistently known in the patient population, nor among the general practitioners across Europe. In the oncologist pool from all countries, access to technologies and agents is also very variable. Scientific principles, methodologies, modes of access as well as the limits of the strategy should therefore be disseminated better in all EU countries and in the different stakeholder populations. There is also a need to develop information platforms where a broad population of patients and healthcare workers easily can access information.
PCM4EU work package 6 is therefore focusing on education and on how to enable access to simple and didactic training on precision cancer medicine both for a broad patient population as well as for practitioners from different EU countries. The team will build and prepare a series of training sessions, both physical meetings and digital events, courses and podcasts. Moreover, work package 6 will provide online tools to guide both patients and physicians on how to access PMC, providing an overview of active programs available in the different countries, strategies to obtain molecular screening, and on how to obtain access to relevant treatment / clinical trials when supported by molecular analysis of the cancer cells.
Information about available training options is published regularly on the PCM4EU training page.