Role of EGFR Mutational Testing in Personalising the Treatment of Non-small-cell Lung Cancer
with EGFR mutations demonstrated a significant improvement in PFS in patients receiving gefitinib.15
Prognostic Utility of Epidermal Growth Factor Receptor (EGFR) Mutational Testing in Patients Who Are Not on EGFR-inhibitor Drugs EGFR mutational testing is usually requested primarily for determining potential response to EGFR-inhibitor drugs. Interestingly, several studies have suggested that even in the absence of EGFR-inhibitor therapy, NSCLC patients with EGFR-positive mutant tumours have a better prognosis than patients with wild-type tumours.16–19
Cost-effectiveness of Molecular Testing to Personalise an Individual Patient’s Treatment The economic value of a well-implemented personalised medicine strategy is based on the assumption that performing relatively inexpensive tests that demonstrate that a specific expensive drug is unlikely to work on a given patient’s tumour will save the overall healthcare industry the high cost of unnecessary and/or ineffective drugs. In addition, considerable cost savings could be realised by not having to manage the many potential side effects and adverse reactions linked to these drugs.
Challenges
Integration of molecular testing into the practice of medicine is not without its challenges. Broad acceptance and adoption is a long-term process. Ongoing research and continuing accumulation of data showing convincing evidence of clinical utility are key elements in gaining wider acceptance of the implementation of personalised medicine and associated molecular oncology tests.
On the laboratory side, high-complexity molecular testing in oncology requires very specialised technical knowledge and skill and a high degree of interpretative capability. Regulatory bodies such as the FDA are increasingly concerned about ensuring that there is sufficient oversight of laboratories that perform these tests.
From a clinical perspective, because these tests can have such a strong influence on treatment decisions, there is a need to ensure that clinicians have a thorough understanding of how best to use the information obtained from molecular testing of the tumours of their patients. To this end, physician education, starting as early as medical school and continuing thereafter, will play a vital role in driving and increasing large-scale understanding and acceptance of molecular oncology tests and their role in personalised medicine for the treatment of cancer.
1. American Cancer Society, Inc., Cancer Facts & Figures, 2009. Available at:
http://www.cancer.org/acs/groups/content/ @nho/documents/document/500809webpdf.pdf
2. 3.
NCI website 2010. Available at:
http://www.cancer.gov/ cancertopics/types/lung
Ries L, et al. (eds.), Cancer Statistics Review, 1975–2002, Bethesda, MD: National Cancer Institute, 2005.
4. Horn L, Pao W, J Clin Oncol, 2009;27(26):4232–5. 5. Sholl LM, et al, Am J Clin Pathol, 2010;133(6):922–34. 6. Travis WD, CAP Today, 2010;24(6). 7. Gridelli C, Curr Opin Oncol, 2009;21:97–8. 8. Tiseo M, et al., Expert Rev Anticancer Ther, 2009;9:425–35.
9.
In terms of reimbursement, the medical insurance industry is a mixed bag at present, with many insurance companies recognising the cost–benefit advantages and clinical utility, and paying for these tests, while others deny claims.
Take-home Messages
EGFR mutational tests are scientifically validated molecular tests for enabling personalised medicine. These tests provide actionable, objective diagnostic results, leading to better outcomes, as NSCLC patients with certain EGFR mutations benefit from treatment with EGFR-TKI drugs such as gefitinib or erlotinib. EGFR mutational status may additionally be useful as a prognostic marker to help determine potential survival irrespective of whether or not the patient is treated with an EGFR-inhibitor drug.
Guidelines for the practice of personalised medicine and associated molecular testing have been issued by organisations such as the FDA, NCCN and ASCO. Although not yet mandated standard of care in the US, as it is in some countries, there is growing support for implementation from regulatory authorities and other organisations.
Significant amounts of money could be saved for the healthcare industry as the cost of a molecular test is far less than the cost of an unnecessary drug being prescribed, not to mention the additional extra costs related to adverse reactions, side effects and associated hospitalisation.
Demand for molecular testing as a means to personalising therapy continues to gain momentum. Innovative diagnostic and therapeutic advances are continuing to be made, offering the potential to improve patient care and bringing new hope to the cancer patient. n
Philip J Ginsburg is Chief Medical Officer and co-founder of AlliedPath, a medical laboratory in San Diego, California, that specialises in personalised medicine molecular diagnostics. He has over 20 years of commercial medical laboratory experience in the US and internationally. He is a former partner and pathologist at Lancet Laboratories, a large premier national laboratory in South Africa. He moved to the US in 1997, where he worked as a medical director at
Quest Diagnostics laboratories and as a consultant for venture capital firms and companies in the pharmaceutical and biotechnology industries. He later accepted a position as senior medical director at Gen-Probe, Inc., a publicly traded molecular diagnostics company, where he provided clinical and strategic leadership for the development and commercialisation of a molecular diagnostic test for prostate cancer. Dr Ginsburg is an accomplished speaker and lecturer, having presented at numerous medical and pharmaceutical conferences worldwide.
Abstracts PRS.4, Soo Lee J, National Cancer Center Korea, Korea; B9.5, Mok T, Hong Kong. 13th World Congress on Lung Cancer, San Francisco, August 2009
10. Ray T, Pharmacogenomics Reporter, May 26, 2010. Available at:
http://www.genomeweb.com/dxpgx/clovis- avila-co-develop-targeted-nsclc-drug-companion-test- deal-worth-209m
11. Ray T, Pharmacogenomics Reporter, 7 April 2010. Available at:
www.genomeweb.com/dxpgx/ astrazeneca-paying-genetic-testing-services-uk-lung- cancer-patients-receiving-ir
12. Ray T, Pharmacogenomics Reporter, 11 November 2009.
Available at:
www.genomeweb.com/dxpgx/fda-top- officials-discuss-ongoing-efforts-bring-agency-genomics- era?page=show
13. American Society of Clinical Oncology, J Clin Oncol, 2009;27:6251–66.
14. Rosell R, et al., N Engl J Med, 2009;361:958–67. 15. Morita S, et al., Clin Cancer Res, 2009;15:4493–8. 16. Eberhard D, et al., J Clin Oncol, 2005;23:1–14. 17. Sasaki H, et al., Int J Cancer, 2006;118:180–84. 18. Marks JL, et al., J Thorac Oncol, 2008;3:111–16. 19. Kosaka T, et al., J Thorac Oncol, 2009;4:22–9.
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