When and how to implement biomarker for cancer care from a French perspec7ve. Fabrice ANDRE Institut Gustave Roussy Villejuif, France

Transcription

1 When and how to implement biomarker for cancer care from a French perspec7ve Fabrice ANDRE Institut Gustave Roussy Villejuif, France

2 Outline Levels of evidence before implemen7ng a biomarker to the daily care Issues in tes*ng and interpreta*on Issues in logis*cs Models for implementa*on of genomic tests at the na*onwide level Conclusion / perspec*ves: Learning cohorts Implementa*on of NGS

3 EGAPP criteria Is the biomarker Associated with different outcome? Retrospec7ve analyses Has the use of biomarker changed the outcome? Randomized trials

4 Prospec7ve trials tes7ng biomarkers in the breast cancer field With the excep7on of few illustra7ve trials (TailorX, MINDACT, RxPONDER) Clinical trials tes7ng biomarkers are not exis7ng in the field of breast cancer What are the other op7ons to validate biomarkers? Dogan, Breast cancer Res Treat, 2013

5 Retrospec7ve studies: Simon- Hayes level of evidence scale Level 1 Consistent Retrospec7ve analyses could be acceptable to define a Level Ib evidence and biomarker implementa7on RM Simon, S Paik, DF Hayes. JNCI, 201:1-7, 2009

6 Prognos7c Value P53 in H&N cancers Limita7ons of retrospec7ve studies: Publica7on biais «consistent studies sugges*ng prognos*c Value for p53» Lack of sta*s*cal significance when unpublished data are added Need to capture and collect all biomarker Studies: WIN registry (Andre, Nature Rev Clin Oncol, 2011) Kyzas P A et al. JNCI J Natl Cancer Inst 2005;97:

7 Limita7ons of retrospec7ve studies: Lack of precise quan7fica7on of biomarker effect Retrospec7ve analyses are not powered enough to detect small differences

8 Early integra*on of biomarkers during phase I/II trials Dogan, Breast cancer Res Treat, 2013

9 Take Home message Randomized trials tes*ng medical usefulness of biomarker is the gold standard but they are not feasible in most of the cases Retrospec*ve analyses of randomized trials provide informa*on about clinical validity but not clinical u*lity Some biomarkers for targeted therapies are developed as companion diagnos*c as soon as phase I trials, but this remains rare Need to find a new model for biomarker valida*on when not feasible in phase I/II trials: Quick access to personalized medicine for pa*ents Precide evalua*on of the medical usefulness

10 Outline Levels of evidence before implemen*ng a biomarker to the daily care Issues in tes7ng and interpreta7on Issues in logis*cs Models for implementa*on of genomic tests at the na*onwide level Conclusion / perspec*ves: Learning cohorts Implementa*on of NGS

11 Issues in tes*ng and interpreta*on Are preanaly*cal steps compa*ble with the test? Need to homogeneize preanaly*cal steps Analy*cal validity? Across *me? Batch effect (PgR, Ibrahim, Am J Clin Pathol. 2008;129(3): ) Issues around cut- off Should grey zones be more frequently used for biomarkers with normal distribu*on? (Goubar, ASCO, 2012) Inter- center reproducibility / centers of exper*se Coordina*on by authori*es Centralized analysis Need to homogeneize processes and limit the variability: Centers of exper7se, coordina7on and single stable technology

12 Outline Levels of evidence before implemen*ng a biomarker to the daily care Issues in tes*ng and interpreta*on Issues in logis7cs Models for implementa*on of genomic tests at the na*onwide level Conclusion / perspec*ves: Learning cohorts Implementa*on of NGS

13 Scenario for genomic tes7ng in the next 10 years Too many tests using too many technologies Need to develop «all- in- one» solu*ons

14 Outline Levels of evidence before implemen*ng a biomarker to the daily care Issues in tes*ng and interpreta*on Issues in logis*cs Models for implementa7on of genomic tests at the na7onwide level Conclusion / perspec*ves: Learning cohorts Implementa*on of NGS

15 Genomic tests: Models of implementa7on Private Biomarker companies Test reimbursed (ex: Genomic Health) Public Hospitals Funding based on nb of tests (ex: French model) Private Biomarker companies Test not reimbursed (ex: NGS facili7es)

16 Implementa7on of genomics in France: A network of 28 public genomic centers 28 genomic centers Deliver results for clinical decision tests in 2010 Yearly funding from French NCI and Ministry of Health (12 M Euros in 2010) Coordina7on of the 28 centers for quality Control, SOP Molecular Epidemiology through single database Added value: equal access to genomic tests for the whole popula7on Keep the «know- how» in the hospitals Generate large molecular epidemiology database Andre F, Clin Cancer Res, 2012, Nowak Nature Rev Clin Oncol, 2012

17 Private companies and genomic tes7ngs for targeted therapies Three prerequisites / issues: Transparent informa*on about level of evidence for efficacy Data sharing and owning Drug access is a major issue Risk: generates a model where pa*ent will have to pay for inves*ga*onal drugs

18 Conclusion: Biomarker Implementa*on Need for new models of biomarker valida*on / implementa*on that would allow quick access to innova*on while valida*ng biomarker: COHORTS Need for coordina*on and stable technology Mul*plicity of tests is not sustainable Need to develop «all- in- one» approaches: High throughput technologies Model of genomic test implementa*on at the level of society should: Allow access to innova*on for the majority of ci*zens While not neglec*ng the freedom to access newer innova*on to individuals Na*onwide genomic programs allow: Wide access and Molecular Epidemiology database NGS by private companies without coordina*on: Is acceptable, in socie*es where health is part of the market, pending transparency about the level of evidence Does not allow datasharing, research informa*on from pa*ent Could distord the field of drug market Which solu7ons to improve the field?

19 Solu7ons: Temporary use of biomarkers in learning cohorts Large cohorts of prospective validation and implementation with reimbursement of the test Coordination to assure high quality Allows: Quick access to the innovation for patients Validation of the test without requiring randomized trials De-reimbursement if the test is not valid Inclusion in databases for research use