Prostate Cancer is the most common cancer in European men. Despite dramatic improvements in early diagnostic and local treatment, one out of five prostate cancer patients will die from their disease. Despite progress in the past years, it remains critical to improve on the present strategy for advanced and metastatic prostate cancer. Within the proposed project, we will evaluate whether intermittent intensified androgen deprivation treatment (iADT) in metastatic prostate cancer is not inferior to continuous treatment in terms of oncological benefit while minimizing side effects and resource utilization and improving patient quality of life. The proposed clinical trial is designed to detect early if iADT has a negative impact on overall survival compared to continuous therapy. If successful, the outcomes of the project will define a new evidence-based standard of care for metastatic hormone sensitive prostate cancer. The proposed research could lead to improved patient survival and quality of life but also improve health system sustainability. This is a multidisciplinary and multistakeholder consortium involving clinical oncologists, surgeons, health economists and patient representatives. The study design was successfully discussed with patients. This action is part of the Cancer Mission cluster of projects on ‘Diagnosis and treatment’.

Colorectal cancer (CRC) is the third most common cancer in Europe with c. 420,000 cases and 150,000 related deaths in 2012. Of total CRC cases, it is estimated that approximately 50-55 % harbour RAS mutations. Current treatment for RAS mutant (mt) metastatic(m) CRC is primarily based on 5-fluoruracil based chemotherapy +/- bevacizumab. However, there are currently limited treatment options once cancers have become resistant. Moreover, while therapy optimization strategies in RAS wild-type CRC patients are feasible, targeted treatment of microsatellite stable (MSS) RAS mt disease is difficult and has not evolved significantly in recent years. COLOSSUS will deliver novel concepts for disease-mechanism based patient stratification in MSS RAS mt mCRC to address the need for stratified or personalised therapeutic interventions in this setting. The consortium will integrate multidimensional and longitudinal omics data to identify new MSS RAS mt specific subtypes with unique signalling dependences. We will harness the power of systems biomedicine, network analysis and computational modelling to identify new actionable pathways, biomarkers and targets across subtypes. These targets will be interrogated in state of the art pre-clinical patient derived xenograft studies. Newly described MSS RAS mt classifiers will be validated as novel patient stratification tools within the COLOSSUS trial. SME partners will develop clinically relevant and commercially viable assays for outcome prediction and stratification of MSS RAS mt patients based on novel classifiers. The impact of assays on CRC associated healthcare costs will further be assessed. Patient associations will be included and the proposal will consider regulatory aspects and commercialisation opportunities, in particular for participating SMEs. mCRC is a complex disease having high prevalence and high economic impact both within a European and global context.

Worldwide, ~7 million women live with or beyond Breast Cancer (BC), as 10-year survival rates exceeding 80% for early-stage (I-III) BC. Premenopausal BC accounts for 25% in the EU and 55% in low/middle income countries. Most premenopausal women with BC have high risk of recurrence, therefore standard treatment includes adjuvant chemo- (CT) and endocrine therapy (ET). However, treatment has substantial physical, emotional and social burden, which is often more pressing for younger compared to older patients. Gene-expression assays are used for post-menopausal patients to identify women who can safely forego CT without detriment on clinical outcomes, preserving Quality of Life (QOL). However, a definitive study has yet to be conducted among premenopausal women with high-risk HR+HER2-BC. The primary objective of PATH-FOR-YOUNG is to conduct a pragmatic randomized controlled trial (RCT) with 5000 patients validating the use of a gene-expression assay to drive adjuvant treatment decisions in this target population. PATH-FOR-YOUNG aims to achieve its objective in 7 years. The project (i) builds on and complements an ongoing twin RCT to ensure timely recruitment, (ii) leverages on a large international consortium of oncologists, pathologists, patient representatives, psychologists, sociologists, ethics and communication experts, biostatisticians, health economists, and technology providers, to assure complementary and multidisciplinary expertise, and (iii) highlights patient-engagement, participatory care, and early involvement of end users. PATH-FOR-YOUNG will also study implementation of digital self-management to support patients throughout the cancer journey and particularly while on ET to improve QOL and medication adherence. A full HTA will ensure a path towards cross-country implementation. PATH-FOR-YOUNG has the ambition to improve BC care, fully integrating the predictive, personalized, preventive, and participatory principles of health management.