Rolling out personalised medicine for cancer in France

Transcription

1 Rolling out personalised medicine for cancer in France Frédérique NOWAK Head of Department for Biology, Transfer & Innovations Institut National du Cancer (INCa) Personalised Medicine Conference ,2 June, Brussels

2 Outline Overall purpose is lead you through the continuous adjustements needed in the organisational framework for personalised medicine in clinical routine in cancer Targeted therapies the starting point for the development of personalised medicine in cancer Organisational framework for PM New treatments & their impact on this framework

3 France National Cancer Institute (INCa) INCa is a National Health and Scientific Agency dedicated to cancer control & reports to the Ministries of Health and of Research. INCa s mission is fulfilled through a systematic implementation of evidence-based strategies across the cancer control continuum (prevention, screening, early detection, diagnosis, treatment, supportive & follow-up care, palliation, and research)

4 Targeted therapies : a change of paradigm for cancer treatment Molecular abnormalities in tumour cells subdivide most frequent cancers in several rare entities gefitinib erlotinib crizotinib Example of Lung cancer? new targeted therapies Different cancer types share the same genetic abnormalities A same targeted therapy can be used to treat different tumor types based on the expression of the molecular target Trastuzumab in breast and gastric cancers expressing HER2

5 Predictive biomarkers for targeted therapies prescription Biomarker Cancer type Targeted therapies Patients nb in 2014 KIT mutations GIST Imatinib 1189 HER2 amplification Breast and gastric cancers Trastuzumab, lapatinib, pertuzumab, trastuzumab emtansine 9680 RAS mutations Colorectal cancer Panitumumab, cetuximab EGFR mutations Lung cancer Gefitinib, erlotinib, afatinib, osimertinib EGFR expression Squamous non small cell lung cancer Necitumumab ALK translocations Lung cancer Crizotinib, ceritinib ROS1 translocations Lung cancer Crizotinib (RTU) 5414 BRAFV600 mutation BCR-ABL translocation 17p deletion / TP53 mutation Melanoma Chronic Myeloid Leukaemia/ Acute Lymphoblastic Leukaemia Chronic Lymphocytic Leukaemia Vemurafenib, dabrafenib, trametinib, cobimetinib 5534 Imatinib, nilotinib, dasatinib, ponatinib, bosutinib 7453 Ibrutinib, idelalisib

6 France organisational framework for personalised medicine Provides nationwide molecular diagnostic tests Objectives 28 regional centers Perform molecular testing for all patients; Whatever the healthcare institution status (public hospitals, private hospitals ); Perform high quality tests; leukemia, solid tumours Partnerships between several laboratories located in University hospitals and cancer centers Regional organization Cooperation between pathologists and biologists x The program is operated by INCa/French Ministry of Health since 2006

7 Nb of patients wirh KRAS tests Benefit & swift access to innovation for all patients Molecular tests are performed : for all patients No charge for patients & hospitals (covered by global budget allocated by INCa & Health Ministry to the centers) with compensation of local pathologists for sample shipments Colorectal cancer : Mid 2008 : EMA approvals of panitumumab and cetuximab for patients with wild type KRAS tumours INCa started funding the 28 centres by the end of 2008 ( 2.5M) x Ensure that all patients actually benefit from molecular testing as soon as a new therapy is available

8 Ensure the best quality for molecular tests Implementation of a quality assurance program Elaboration of guidelines for : the detection of mutations in solid tumours ; the organisation of molecular testing ; reports of molecular tests Implementation of national External Quality Assessment rounds for the main tests in the 28 centers x Towards ISO accreditation

9 Increasing number of actionable molecular alterations & NGS BRAF PDK1 HER2 KDR STK11 Lung cancer NRAS ALK EGFR PI3K MET TOP1 FGFR4 ALK (ampl) KRAS No mutation Challenge : switch from the one by one approach to the targeted NGS approach NGS increases probability for a given patient to identify an actionable mutation in his tumour Increase the access to innovative drugs within the framework of clinical trials Facilitate the development of new targeted therapies NGS blurs the frontier between care & clinical research

10 Targeted NGS in routine practice Pilot phase launched in 2013 with 11 molecular genetic centres : develop the necessary skills to use this new technology Monitoring led by INCa : increase the sharing of experiences Draft guidelines 5 referent teams in bioinformatics : Validate & release existing data analysis pipelines, or develop better ones support wet labs and their embedded bioinformaticians through network animation and training Economic impact of NGS evaluated at the same time Rolling out started in 2015 in all the molecular centres Progressive shift from the standard approach towards targeted NGS for all patients This objective should be achieved by the end of 2016

11 Economic issues Molecular screening allows the optimisation of treatments & expenditures Molecular test (targeted NGS + FISH + IHC) 1000 Targeted therapy 3000 / month For a non responder 6000 (2 months) For a responder 36,000 (12 months) Cost of molecular tests << cost of targeted therapies

12 Economic issues Cost of cancer drugs in 2014 in France : 3.6 billions Source : Rapport Thérapies ciblées, INCa % compared to 2013 Main causes of steady increases of targeted therapies expenditures : Targeted therapies available for new subsets of patients Drugs combinations Patients stay longer under treatment Targeted therapies 1.7 billions 47% of total cost

13 Change of paradigm in cancer treatment : a fast evolving scientific and medical environment Targeted therapies Molecular analysis of tumour cells PARP inhibitors Germline genetics analysis New challenges : 2014 : Market autorisation of olaparib in ovarian cancer for patients with BRCA mutations (either somatic or germline) 1. Patients information on the personal and familial impact of a positive BRCA test : ethics Molecular tests integrating 3 complementary expertises : pathology, somatic genetics and germline genetics Need to make current organisational framework evolve

14 French organisational framework for germline genetics in oncology Objectives : identify people with genetic predisposition to cancer offer specific prevention programmes including risk-adjusted screening, preventive surgery and medicines. 130 genetic counseling sites in 90 cities 25 laboratories for genetic testing Perform genetic tests prescribed by clinical geneticists Boulogne-sur-Mer Lille (2) Centre Oscar Lambret, Lille CHU de Lille Lens Valenciennes Brest Saint-Brieuc LorientVannes Saint-Nazaire Cherbourg La Rochelle Bordeaux (2) Le Havre Caen Rennes (2) (2) Le Mans Angers (2) Cholet Nantes (2) Niort Angoulême Tours Poitiers Amiens Rouen Troyes Montargis Orléans Auxerre Bourges Reims (4) Clermont-Ferrand (2) Limoges (2) Saint-Etienne Aurillac Charleville Mézières Mâcon Dijon (2) Metz Chalon-sur-Saône Lyon (7) Valence Nancy (2) Besançon Chambéry Grenoble (2) Gap Strasbourg (3) Colmar Mulhouse Belfort-Montbéliard Thonon-les-Bains CHU de Rennes Institut Bergonié, Bordeaux CHU de Rouen Centre François Baclesse, Caen CHU de Nantes CHU d Angers Centre Jean Perrin, Clermont-Ferrand CHU-CLCC de Reims CHU de Nancy Centre Georges-François Leclerc, Dijon CHU de Lyon cancers non fréquents CHU-CLCC de Lyon cancers fréquents Centre Paul Strauss, Strasbourg CHU de Strasbourg Bayonne Toulouse (3) Tarbes Rodez Avignon Nîmes Grasse Nice Aix-en-Provence Montpellier (2) Draguignan Martigues Aubagne Béziers Marseille Toulon Bastia (3) Corté Perpignan CHU de Montpellier APHM Institut Claudius Regaud, Toulouse Institut Paoli Calmettes, Marseille Ajaccio Clichy Levallois-Perret Saint-Cloud Briis-sous-Forges Bobigny Bondy (2) Paris (13) Kremlin Bicêtre Villejuif Corbeil-Essonnes Pointe à Pitre Saint-Denis Sainte-Clotilde Fort de France Cayenne Bonifacio Paris Institut Gustave Roussy, Villejuif APHP Hôpitaux Universitaires La Pitié-Salpêtrière APHP Hôpitaux Universitaires Paris Nord Val de Seine APHP Hôpitaux Universitaires Paris Centre et Paris Ouest Institut Curie Saint-Pierre

15 Towards a more integrated organisational framework Pathology Somatic genetics Molecular genetics centres Germline genetics Oncogenetic programme : genetic counseling and laboratories

16 Towards a more integrated organisational framework Pathology Somatic genetics Integrated organisational framework Germline genetics

17 Targeted therapies Molecular analysis of tumour cells Immunotherapy Checkpoint inhibitors : Anti-CTLA4 Anti-PD1 and anti-pdl1 Change of paradigm in cancer treatment : a fast evolving scientific and medical environment Market authorization and ongoing clinical trials in melanoma, lung cancer, mesothelioma, kidney cancer, bladder cancer. PARP inhibitors Germline genetics analysis => Specific predictive biomarkers are under development and will enter soon into clinical practice

18 Towards next ajustment integrated of the organisational framework Pathology Somatic genetics Germline genetics Immunotherapy

19 Conclusion France organisational framework for precision medicine in oncology : has been operating for 7 years; offers an equal access to molecular testing for all patients in France; shows that molecular stratification can be successfully integrated into the healthcare system; shows that such a national organisation has to be continuously adjusted in a context of a fast evolving scientific, medical and technological environment

20 plus d informations sur e-cancer.fr Institut national du cancer 52, avenue André Morizet Boulogne-Billancourt Cedex France Tél. +33 (0) e-cancer.fr