EuroBioForum 2012 | 18 April 2012 Presentation by Frédérique Nowak, Head of Pathology and Genetics, French National Cancer Institute

1. Personalized Medicine:
A nationwide initiative for an equal access to cancer
treatment in France
Frédérique Nowak
Institut National du Cancer – 18/04/2012

2. Institut national du cancer (INCa)
• The French National Cancer Institute is a health and science agency
dedicated to oncology.
• INCa was created through the Public Health Act of 9 August 2004
• INCa is involved in all aspects of the fight:
- Public health : Observation – Prevention - Screening
- Care: Improve the quality of care for all cancer patients
- Research: Orient the national cancer policy towards
international competition
- Information: Give every individual the means to help fight
cancer
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3. The cancer plan 2009-2013
The Cancer Plan 2009-2013:
• follows on from the Cancer Plan 2003-2007
• 5 areas :
 Research
 Observation
 Prevention-screening
 Patient care
 Life during and after cancer
• 30 measures/ 118 actions
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4. The shift of paradigm for cancer treatment
 Towards molecular subsets of cancers
 Molecular genetics deciphers severe frequent cancers into specific rare cancers
Molecular subsets of non
small cell lung cancer :
20,000 patients
 Molecular alterations shared in several cancers
 One drug is now efficient for the treatment of several « rare cancers »
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5. Predictive tests for targeted therapies
prescription
Imatinib prescription
BCR-ABL translocation:
Chronic Myeloïd Leukemia/ 1- Imatinib prescription
1- BCR-ABL detection
Acute Lymphoblastic 2- Monitoring of minimal residual
2- BCR-ABL quantification
Leukemia disease
3- ABL mutation
3- Resistance to Imatinib
KIT and PDGFRA
GIST Imatinib prescription
mutations
HER2 amplification Breast and gastric cancers Trastuzumab prescription
Panitumumab and cetuximab
KRAS mutations Colorectal cancer
prescription
EGFR mutations Lung cancer Gefitinib and erlotinib prescription
ALK translocations Lung cancer Crizotinib prescription
BRAFV600 mutation Melanoma Vemurafenib prescription
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6. Ensuring equity of access to innovation:
France organisation of molecular centres for personalized
medicine
Provides nationwide molecular diagnostic tests
The programme is operated by the INCa/Ministry of Health since 2006 St Cloud/
Versailles •
• Paris (2) : AP-HP, Curie
•
Villejuif
 Objectives  28 regional centres • Lille
 Perform molecular testing  Partnerships between • Rouen
Caen • • Reims
for all patients; several laboratories located Brest
•
• Nancy
• Strasbourg
Mulhouse/
Rennes • Colmar
 Whatever the healthcare in University hospitals and • Angers
• Tours • Dijon
• Nantes • Besançon
institution status (public cancer centres • Poitiers
hospitals, private • Limoges • Clermont • Lyon
 Regional organization Ferrand • St Etienne
• Grenoble
hospitals…); Bordeaux •
 Perform high quality tests;  Cooperation between Toulouse •
Montpellier/
• Marseille
• Nice
Nîmes •
pathologists and biologists
 leukemia, solid tumours
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7. Benefit for all patients
Molecular tests are performed :
 For all patients
 free of charge for patients & hospitals
 With compensation of local
pathologists for sample shipments
 Ensure that all patients effectively benefit
from molecular testing
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8. Rapid access to innovation: EGFR testing in lung
cancer
June 2009 : gefitinib approvals by EMA for patients with activating mutations of
EGFR in their tumours
 Mutations : 9,6%
 60 % of external prescriptions
20761
 Median time for results : 7 days
20000
16834
Nombre de patients
 Non contributive results :
Non contributive results (%)
10000
5,2%
5,0
2667 3,7%
1269
0 1,5%
2008 2009 2010 2011
0,0
non amplifiable depleted sample Rate of tumor cells
DNA below detection
thresold

9. Funding mechanisms
Offer the best treatment to patients considering the cost – effectiveness ratio
 Seed fundings from INCa for the test set-up
 Performance and cost evaluation
 Recurrent annual fundings from the French Ministry of Health insurance
This programme benefits also from INCa/private partnerships
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10. Example of gefitinib treatment : €69M spared
cost for the health insurance
EGFR testing for lung cancer patients
€ 1.7M
15 000 patients - 1 724 patients +
(gefinitib treatment:
(gefinitib treatment:
8 weeks DFS; Mok 2009)
38 weeks DFS; Mok 2009)
€ 69M € 35M
Cost of gefitinib treatment
Spared cost of gefitinib treatment 10

11. Ensure the best quality for molecular tests
Implementation of a quality assurance programme
• Elaboration of guidelines for:
- the detection of mutations in solid tumors;
- the organization of molecular testing;
- Reports of molecular tests
• Implementation in 2011 of a national External Quality
Assessment for the 28 centres (BCR-ABL, KRAS, EGFR)
 Assurance quality optimization
 guide the molecular genetics centres to becoming accredited to
ISO 15189 standard as soon as possible
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12. A new approach for rapid access to
targeted therapies
Biomarkers for targeted therapies currently
evaluated in clinical trials (Phases I to III) :
Cancer Molecular target
EGFR mutations
KRAS mutations
HER2 mutations
Lung
BRAF mutation
PI3KCA mutations
ALK translocations
KRAS mutations
Colon - rectum BRAF mutations
microsatellite instability if < 60 years
BRAF mutations
Melanoma
KIT mutations

13. Anticipate the launch of new molecules
The INCa allocated €3.5M in 2010 and €2.8M in 2011 for the prospective detection
of emerging biomarkers
 For the 20,000 patients with lung adenocarcinoma,
additional analysis of :
- EGFR mutations conferring resistance to TKI-EGFR;
- KRAS, HER2, PI3KCA and BRAF mutations;
- ALK translocation.
 For the 17,000 patients with colorectal cancer,
additional analysis of :
- BRAF mutation;
- MSI test.
 BRAF and cKIT mutations for patients with melanoma
 Be ready to perform the test as soon as the therapy is available

14. Improve interface with research
Make the most of the generated data=> implementation of a lung cancer
database :
 funded by INCa, coordinated by IFCT (Intergroupe Français de Cancérologie
Thoracique) and molecular genetics centres representatives
 evaluate the correlation between molecular alteration identification and targeted
therapy prescription
 collect both clinical data, molecular data and clinical follow up of patients
Improve interfaces with clinical research
Potential evolution of their mission : molecular genetics centres could
become testing laboratories for clinical trials
Improve interfaces with translational research
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15. An expanding list of predictive tests
 Towards an « all in one approach »: implementation of next generation sequencing techniques
for clinical diagnostics

16. Conclusions and perspectives
o This initiative for targeted cancer treatment in France shows that :
 innovation can be successfully integrated into the healthcare system
 molecular stratification is cost effective
 this organization could be easily expanded in other european settings
o These molecular genetics centres are key to help develop translationnal
research and to sustain progress
o They are instrumental to facilitate access to the best care and improve
patient’s survival and quality of life
o Training of medical students and professionals to personalised medicine
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