The drivers of precision medicine are clear: for patients (and physicians) - more options, durable clinical benefit, reduced exposure to non-effective drugs and potential to leverage current scientific and technological advances; for the pharmaceutical industry - the potential to tackle core challenges in discovering and developing better and more efficacious medicines, to reduce rates of attrition in drug development and to reduce development costs; for healthcare systems and payers - improved efficiency through the provision of effective care and avoiding ineffective treatments. Oncology has been at the vanguard, the improvements gained in patient survival notable. However, the increasing number of molecular subgroups requires an equally increasing number (and new generation) of highly selective agents targeting inevitably lower incidence molecular segments. Innovative trial designs (umbrella/basket studies) are emerging as a patient-centric approach to drug development, and the rise in public-private partnerships, cross-industry, government and non-profit sector collaborations is enabling implementation of complex clinical trial designs. This poses significant challenges for healthcare systems and regulatory approval. Further substantial evolution of policy and processes, particularly regulatory requirements for approval for new therapeutics, are required.

Green ED, Guyer MS; National Human Genome Research Institute: Charting a course for genomic medicine from base pairs to bedside. Nature 2011;470:204-213.
Association of the British Pharmaceutical Industry: The Stratification of Disease for Personalised Medicines. London, Association of the British Pharmaceutical Industry, 2014.
Academy of Medical Science: Realising the Potential of Stratified Medicine. London, Academy of Medical Science, 2013.
Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, Pangalos MN: Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework. Nat Rev Drug Discov 2014;13:419-431.
Tsimberidou A-M, Iskander NG, Hong DS, Wheler JJ, Falchook GS, Fu S, Piha-Paul S, Naing A, Janku F, Luthra R: Personalized medicine in a phase I clinical trials program: The MD Anderson Cancer Center initiative. Clin Cancer Res 2012;18:6373-6383.
Hollebecque A, Massard C, De Baere T, Auger N, Lacroix L, Koubi-Pick V, Vielh P, Lazar V, Bahleda R, Ngo-Camus M: Molecular screening for cancer treatment optimization (MOSCATO 01): a prospective molecular triage trial-interim results (abstract). J Clin Oncol 2013;31(suppl):2512.
Dienstmann R, Serpico D, Rodon J, Saura C, Macarulla T, Elez E, Alsina M, Capdevila J, Perez-Garcia J, Sánchez-Ollé G: Molecular profiling of patients with colorectal cancer and matched targeted therapy in phase I clinical trials. Mol Cancer Ther 2012;11:2062-2071.
Kim ES, Herbst RS, Wistuba II, Lee JJ, Blumenschein GR, Tsao A, Stewart DJ, Hicks ME, Erasmus J, Gupta S: The battle trial: personalizing therapy for lung cancer. Cancer Discov 2011;1:44-53.
Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, Hudis C, Gray JW, Perou C, Yau C: Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL-CALGB 150007/150012, ACRIN 6657. J Clin Oncol 2012;30:3242-3249.
Esserman LJ, Berry DA, Cheang MC, Yau C, Perou CM, Carey L, DeMichele A, Gray JW, Conway-Dorsey K, Lenburg ME: Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 trial (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat 2012;132:1049-1062.
Hylton NM, Blume JD, Bernreuter WK, Pisano ED, Rosen MA, Morris EA, Weatherall PT, Lehman CD, Newstead GM, Polin S: Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy - results from ACRIN 6657/I-SPY trial. Radiology 2012;263:663-672.
Lin C, Buxton MB, Moore D, Krontiras H, Carey L, DeMichele A, Montgomery L, Tripathy D, Lehman C, Liu M: Locally advanced breast cancers are more likely to present as interval cancers: results from the I-SPY 1 trial (CALGB 150007/150012, ACRIN 6657, Interspore Trial). Breast Cancer Res Treat 2012;132:871-879.
Lindsay CR, Shaw E, Walker I, Johnson PW: Lessons for molecular diagnostics in oncology from the Cancer Research UK Stratified Medicine Programme. Expert Rev Mol Diagn 2015;15:287-289.
Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-2388.
Jänne PA, Yang JC-H, Kim D-W, Planchard D, Ohe Y, Ramalingam SS, Ahn M-J, Kim S-W, Su W-C, Horn L: AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med 2015;372:1689-1699.
US Food and Drug Administration: Nucleic Acid Based Tests. Silver Spring, US Food and Drug Administration, 2015.
US Food and Drug Administration: List of Cleared or Approved Companion Diagnostic Devices (in vitro and Imaging Tools). Silver Spring, US Food and Drug Administration, 2015.
US Food and Drug Administration: Drug Approvals and Databases. Silver Spring, US Food and Drug Administration, 2015.
European Medicines Agency: Approvals. London, European Medicines Agency, 2015.
Chantrill LA, Nagrial AM, Watson C, Johns AL, Martyn-Smith M, Simpson S, Mead S, Jones MD, Samra JS, Gill AJ: Precision medicine for advanced pancreas cancer: the individualized molecular pancreatic cancer therapy (IMPACT) trial. Clin Cancer Res 2015;21:2029-2037.
US National Cancer Institute: NCI-Match (Molecular Analysis for Therapy Choice). Rockville, US National Cancer Institute, 2015.
Lung Cancer Master Protocol (Lung-MAP) Clinical Trials: Lung-Map - The Lung Cancer Master Protocol 2013.
EORTC: Colorectal Cancer Screening Platform: SPECTAcolor. Brussels, EORTC, 2015.
EORTC: Colorectal Cancer Screening Platform: SPECTAlung. Brussels, EORTC, 2015.
Zardavas D, Maetens M, Irrthum A, Goulioti T, Engelen K, Fumagalli D, Salgado R, Aftimos P, Saini K, Sotiriou C: The AURORA initiative for metastatic breast cancer. Br J Cancer 2014;111:1881-1887.
Peel N: Stratified medicine and the lung cancer ‘matrix' trial - part of a cancer care revolution. Cancer Research UK Science Blog, 2014.
Pancreatic Cancer Action Network: Know Your Tumor. Manhattan Beach, Pancreatic Cancer Action Network, 2015.
FoundationOne: What Is FoundationOne? Cambridge, FoundationOne, 2015.
Foundation Medicine: Learn More about Cancer and Available Treatment Options. Cambridge, Foundation Medicine, 2015.
Perthera: Personalized Cancer Therapy. McLean, Perthera, 2015.
Worldwide Innovative Networking: Worldwide Innovative Networking in Personalised Cancer Medicine. Villejuif, Worldwide Innovative Networking, 2015.
Simon R, Roychowdhury S: Implementing personalized cancer genomics in clinical trials. Nat Rev Drug Discov 2013;12:358-369.
Waddell N, Pajic M, Patch A-M, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K: Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015;518:495-501.
Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, Schnall-Levin M, White J, Sanford EM, An P: Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol 2013;31:1023-1031.
Dawson S-J, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin S-F, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B: Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 2013;368:1199-1209.
Douillard J-Y, Ostoros G, Cobo M, Ciuleanu T, Cole R, McWalter G, Walker J, Dearden S, Webster A, Milenkova T: Gefitinib treatment in EGFR mutated Caucasian NSCLC: circulating-free tumor DNA as a surrogate for determination of EGFR status. J Thorac Oncol 2014;9:1345.
Chang DK, Grimmond SM, Evans TJ, Biankin AV: Mining the genomes of exceptional responders. Nat Rev Cancer 2014;14:291-292.
Lewin J, Siu LL: Cancer genomics: the challenge of drug accessibility. Curr Opin Oncol 2015;27:250-257.
Lara PN, Higdon R, Lim N, Kwan K, Tanaka M, Lau DH, Wun T, Welborn J, Meyers FJ, Christensen S: Prospective evaluation of cancer clinical trial accrual patterns: identifying potential barriers to enrollment. J Clin Oncol 2001;19:1728-1733.
English R, Lebovitz Y, Griffin R: Forum on Drug Discovery, Development, and Translation. Transforming Clinical Research in the United States: Challenges and Opportunities: Workshop Summary. Washington, National Academies Press, 2010.
Yap TA, Sandhu SK, Workman P, de Bono JS: Envisioning the future of early anticancer drug development. Nat Rev Cancer 2010;10:514-523.
Mandrekar SJ, Sargent DJ: Clinical trial designs for predictive biomarker validation: theoretical considerations and practical challenges. J Clin Oncol 2009;27:4027-4034.
Printz C: Failure rate: why many cancer drugs don't receive FDA approval, and what can be done about it. Cancer 2015;121:1529-1530.
Sleijfer S, Bogaerts J, Siu LL: Designing transformative clinical trials in the cancer genome era. J Clin Oncol 2013;31:1834-1841.
Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J: Clinical development success rates for investigational drugs. Nat Biotechnol 2014;32:40-51.
US Food and Drug Administration: Food and Drug Administration Safety and Innovation Act (FDASIA). Silver Spring, US Food and Drug Administration, 2015.
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