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Tumour molecular profiling for deciding therapy—the French initiative

Nature Reviews Clinical Oncology volume 9, pages 479–486 (2012)Cite this article

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Abstract

The use of tumour molecular profiles for therapeutic decision making requires that molecular diagnostics be introduced into routine clinical practice. To this end, the French National Cancer Institute and French Ministry of Health have set up a national network of 28 regional molecular genetics centres. These facilities perform selected molecular tests, free of charge, for all patients in their region, regardless of the institution where they are treated. A specific programme has also been implemented to anticipate the launch of new targeted treatments and reduce time-to-access to new drugs and experimental therapies. In 2011, 55,000 patients with cancer in France benefited from molecular predictive tests. The French nationwide initiative for tumour molecular profiling is a tool to fight inequalities in access to molecular testing and targeted therapy, and demonstrates that molecular stratification of tumours for therapeutic decisions is a cost-effective strategy that can be successfully integrated into the health-care system.

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Figure 1: The location of molecular genetics centres in France.
Figure 2: Predictive molecular testing activity in France 2007–2011.

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References

  1. Torkamani, A., Verkhivker, G. & Schork, N. J. Cancer driver mutations in protein kinase genes. Cancer Lett. 281, 117–127 (2009).

    Article  CAS  Google Scholar 

  2. Hochhaus, A. et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 23, 1054–1061 (2009).

    Article  CAS  Google Scholar 

  3. Blanke, C. D. et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J. Clin. Oncol. 26, 626–632 (2008).

    Article  CAS  Google Scholar 

  4. Verweij, J. et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 364, 1127–1134 (2004).

    Article  CAS  Google Scholar 

  5. Bang, Y. J. et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376, 687–697 (2010).

    Article  CAS  Google Scholar 

  6. Douillard, J. Y. et al., Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. J. Clin. Oncol. 28, 744–752 (2010).

    Article  CAS  Google Scholar 

  7. Mok, T. S. et al. Randomized, placebo-controlled, phase II study of sequential erlotinib and chemotherapy as first-line treatment for advanced non-small-cell lung cancer. J. Clin. Oncol. 27, 5080–5087 (2009).

    Article  CAS  Google Scholar 

  8. Piccart-Gebhart, M. J. et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. 353, 1659–1672 (2005).

    CAS  Google Scholar 

  9. Van Cutsem, E. et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N. Engl. J. Med. 360, 1408–1417 (2009).

    Article  CAS  Google Scholar 

  10. Van Cutsem, E. et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J. Clin. Oncol. 29, 2011–2019 (2011).

    Article  CAS  Google Scholar 

  11. Vogel, C. L. et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J. Clin. Oncol. 20, 719–726 (2002).

    Article  CAS  Google Scholar 

  12. European Medicines Agency [online], (2012).

  13. Blanchon, F. et al. Epidemiologic of primary bronchial carcinoma management in the general French hospital centers [French]. Rev. Mal. Respir. 19, 727–734 (2002).

    CAS  PubMed  Google Scholar 

  14. Grivaux, M. et al. Five year survival for lung cancer patients managed in general hospitals [French]. Rev. Mal. Respir. 26, 37–44 (2009).

    Article  CAS  Google Scholar 

  15. Étude des Registres de Cancers du Réseau Francim. Survie des patients atteints de cancer en France [French]. (Springer, Paris, 2007).

  16. Institut de Veille Sanitaire. Projections de L'incidence et de la Mortalité par Cancer en France en 2011. Rapport technique [French]. (Saint Maurice, 2011).

  17. European Commission. Enterprise and Industry: CE marking [online], (2012).

  18. European Commission. DG Health & Consumers: Medical devices [online], (2012)

  19. Moelans, C. B., de Weger, R. A. Van der Wall, E. & van Diest, P. J. Current technologies for HER2 testing in breast cancer. Crit. Rev. Oncol. Hematol. 80, 380–392 (2011).

    Article  CAS  Google Scholar 

  20. Tsiatis, A. C. et al. Comparison of Sanger sequencing, pyrosequencing, and melting curve analysis for the detection of KRAS mutations: diagnostic and clinical implications. J. Mol. Diagn. 12, 425–432 (2010).

    Article  CAS  Google Scholar 

  21. Ma, E. S., Wong, C. L., Law, F. B., Chan, W. K. & Siu, D. Detection of KRAS mutations in colorectal cancer by high-resolution melting analysis. J. Clin. Pathol. 62, 886–891 (2009).

    Article  CAS  Google Scholar 

  22. Magnin, S. et al. A multiplex SNaPshot assay as a rapid method for detecting KRAS and BRAF mutations in advanced colorectal cancers. J. Mol. Diagn. 13, 485–492 (2011).

    Article  CAS  Google Scholar 

  23. Sundström, M. et al. KRAS analysis in colorectal carcinoma: analytical aspects of Pyrosequencing and allele-specific PCR in clinical practice. BMC Cancer 10, 660 (2010).

    Article  Google Scholar 

  24. Amado, R. G. et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 26, 1626–1634 (2008).

    CAS  Google Scholar 

  25. Karapetis, C. S. et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med. 359, 1757–1765 (2008).

    Article  CAS  Google Scholar 

  26. Sharma, S. V., Bell, D. W., Settleman, J. & Haber, D. A. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer 7, 169–181 (2007).

    Article  CAS  Google Scholar 

  27. Kancha, R. K., Peschel, C. & Duyster, J. The epidermal growth factor receptor-L861Q mutation increases kinase activity without leading to enhanced sensitivity toward epidermal growth factor receptor kinase inhibitors. J. Thorac. Oncol. 6, 387–392 (2011).

    Article  Google Scholar 

  28. Loupakis, F. et al. KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br. J. Cancer 101, 715–721 (2009).

    Article  CAS  Google Scholar 

  29. Rouleau, E. et al. KRAS mutation status in colorectal cancer to predict response to EGFR targeted therapies: the need for a more precise definition. Br. J. Cancer 99, 2100 (2008).

    Article  CAS  Google Scholar 

  30. Yasuda, H., Kobayashi, S. & Costa, D. B. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol. 13, e23–31 (2011).

    Article  Google Scholar 

  31. Zhou, Q. et al. Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer. J. Clin. Oncol. 29, 3316–3321 (2011).

    Article  CAS  Google Scholar 

  32. Gow, C. H. et al. Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. Ann. Oncol. 20, 696–702 (2009).

    Article  Google Scholar 

  33. Park, S. et al. Discordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer. J. Thorac. Oncol. 4, 809–815 (2009).

    Article  Google Scholar 

  34. Sun, L. et al. Comparison of KRAS and EGFR gene status between primary non-small cell lung cancer and local lymph node metastases: implications for clinical practice. J. Exp. Clin. Cancer Res. 30, 30 (2011).

    Article  CAS  Google Scholar 

  35. Chapman, P. B. et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364, 2507–2516 (2011).

    Article  CAS  Google Scholar 

  36. Kwak, E. L. et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med. 363, 1693–1703 (2010).

    Article  CAS  Google Scholar 

  37. Pao, W. & Girard, N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 12, 175–180 (2011).

    Article  CAS  Google Scholar 

  38. Institut National du Cancer. Découvrez le site du Plan cancer 2009-2013. [French] (2012).

  39. Contre le Cancer. La réponse de François Hollande à la ligue Contre le Cancer. (2012).

  40. Intergroupe Francophone de Cancérologie Thoracique. Biomarqueurs France [online], (2012).

  41. Jabbour, E. et al. Practical advice for determining the role of BCR-ABL mutations in guiding tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia. Cancer 117, 1800–1811 (2011).

    Article  CAS  Google Scholar 

  42. Institut National du Cancer. Cancer du Poumon—Bilan Initial [French] (Boulogne–Billancourt, 2011).

  43. Rosell, R. et al. Screening for epidermal growth factor receptor mutations in lung cancer. N. Engl. J. Med. 361, 958–967 (2009).

    Article  CAS  Google Scholar 

  44. Sekine, I., Yamamoto, N., Nishio, K. & Saijo, N. Emerging ethnic differences in lung cancer therapy. Br. J. Cancer 99, 1757–1762 (2008).

    Article  CAS  Google Scholar 

  45. Elkin, E. B. et al. HER-2 testing and trastuzumab therapy for metastatic breast cancer: a cost-effectiveness analysis. J. Clin. Oncol. 22, 854–863 (2004).

    Article  Google Scholar 

  46. Blank, P. R., Moch, H., Szucs, T. D. & Schwenkglenks, M. KRAS and BRAF mutation analysis in metastatic colorectal cancer: a cost-effectiveness analysis from a Swiss perspective. Clin. Cancer Res. 17, 6338–6346 (2011).

    Article  CAS  Google Scholar 

  47. Mancl, E. E., Kolesar, J. M. & Vermeulen, L. C. Clinical and economic value of screening for Kras mutations as predictors of response to epidermal growth factor receptor inhibitors. Am. J. Health Syst. Pharm. 66, 2105–2112 (2009).

    Article  Google Scholar 

  48. Borget, I. et al. Comparative cost-effectiveness of three strategies for guiding second-line erlotinib initiation in non small-cell lung cancer: a French prospective multicenter study (ERMETIC Project Part 3). Eur. Respir. J. 39, 172–179 (2012).

    Article  CAS  Google Scholar 

  49. de Lima Lopes, G. Jr et al. Cost-effectiveness of epidermal growth factor receptor mutation testing and first-line treatment with gefitinib for patients with advanced adenocarcinoma of the lung. Cancer 118, 1032–1039 (2011).

    Article  Google Scholar 

  50. Cancer Research UK. Stratified medicine programme [online], (2012).

  51. Andre, F. et al. Molecular characterization of breast cancer with high-resolution oligonucleotide comparative genomic hybridization array. Clin. Cancer Res. 15, 441–451 (2009).

    Article  CAS  Google Scholar 

  52. Gong, Y. et al. Determination of oestrogen-receptor status and ERBB2 status of breast carcinoma: a gene-expression profiling study. Lancet Oncol. 8, 203–211 (2007).

    Article  CAS  Google Scholar 

  53. Lipson, D. et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat. Med. 18, 382–384 (2012)

    Article  CAS  Google Scholar 

  54. MacConaill, L. E. et al. Profiling critical cancer gene mutations in clinical tumor samples. PLoS ONE 4, e7887 (2009).

    Article  Google Scholar 

  55. Cronin, M. & Ross, J. S. Comprehensive next-generation cancer genome sequencing in the era of targeted therapy and personalized oncology. Biomark. Med. 5, 293–305 (2011).

    Article  CAS  Google Scholar 

  56. Jones, S. J. et al. Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors. Genome Biol. 11, R82 (2010).

    Article  Google Scholar 

  57. Ley, T. J. et al. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 456, 66–72 (2008).

    Article  CAS  Google Scholar 

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Acknowledgements

We wish to thank M. P. Gaub, J. P. Ghnassia, J. P. Merlio, A. Tchirkov, M. L. Kottler, F. Piard, J. F. Abgrall, T. Fest, J. C. Pagès, C. Clavel, C. Mougin, J. C. Sabourin, J. M. Bidart, O. Delattre, I. Bièche, M. Marty, P. Laurent-Puig, T. Molina, T. Maudelonde, F. Labrousse, J. Feuillard, P. Jonveaux, E. Delabesse, N. Porchet, H. Avet-Loiseau, M. Denis, A. Morel, P. Reynier, A. Turhan, L. Karayan-Tapon, F. Pedeutour, J. Gabert, J. Y. Scoazec, D. Leroux, L. Campos and the staff of the 28 molecular genetics centres, J. Blin, E. Lonchamp and B. Mourlat of INCa, the previous president of INCa, D. Maraninchi, and the current president of INCa, A. Buzyn.

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  1. Direction de la Recherche et de l'Innovation, Institut National du Cancer, 52 Avenue André Morizet, Boulogne Billancourt 92153, France,

    Frédérique Nowak & Fabien Calvo

  2. Department of Medicine, Institut Gustave-Roussy, 114 rue Edouard Vaillant, Villejuif, 94805, France

    Jean-Charles Soria

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  1. Frédérique Nowak
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All authors researched data for the article, made a considerable contribution to the discussion of the content, wrote the manuscript and edited and revised the article before submission.

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Correspondence to Fabien Calvo.

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Nowak, F., Soria, JC. & Calvo, F. Tumour molecular profiling for deciding therapy—the French initiative. Nat Rev Clin Oncol 9, 479–486 (2012). https://doi.org/10.1038/nrclinonc.2012.42

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