Molecular biomarkers and precision medicine in colorectal cancer: a systematic review of health economic analyses

Raymond Henderson _, Declan French, Richard Sullivan, Tim Maughan, Mike Clarke and Mark Lawler

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Oncotarget. 2019; 10:3408-3423. https://doi.org/10.18632/oncotarget.26909

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Raymond Henderson1,2, Declan French2, Richard Sullivan3, Tim Maughan4, Mike Clarke5 and Mark Lawler1

1 Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, United Kingdom

2 Queen’s Management School, Queen’s University Belfast, Belfast, United Kingdom

3 Institute of Cancer Policy, King's College London and King’s Health Partners Comprehensive Cancer Centre, London, United Kingdom

4 CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom

5 Centre for Public Health, Queen’s University Belfast, Belfast, United Kingdom

Correspondence to:

Raymond Henderson,email: [email protected]

Keywords: economic analysis; precision medicine; colorectal cancer; biomarker; KRAS

Received: March 25, 2019     Accepted: April 21, 2019     Published: May 21, 2019


An increased understanding of the biology of colorectal cancer (CRC) has fuelled identification of biomarkers with potential to drive a stratified precision medicine care approach in this common malignancy.

We conducted a systematic review of health economic assessments of molecular biomarkers (MBMs) and their employment in patient stratification in CRC. Our analysis revealed scenarios where health economic analyses have been applied to evaluate the cost effectiveness of MBM-guided clinical interventions: (i) evaluation of Dihydropyrimidine dehydrogenase gene (DPYD) status to identify patients susceptible to 5-Fluouracil toxicity; (ii) determination of Uridine 5′-diphospho- glucuronosyltransferase family 1 member A1 gene (UGT1A1) polymorphism status to help guide irinotecan treatment; (iii) assessment of RAS/RAF mutational status to stratify patients for chemotherapy or Epidermal Growth Factor Receptor (EGFR) therapy and (iv) multigene expression analysis (Oncotype Dx) to identify and spare non-responders the debilitating effects of particular chemotherapy interventions.

Our findings indicate that Oncotype Dx is cost-effective in high income settings within specific price points, by limiting treatment toxicity in CRC patients. DPYD status testing may also be cost effective in certain settings to avoid specific 5-FU toxicities post treatment. In contrast, current research does not support UGT1A1 polymorphism status as a cost-effective guide to irinotecan dosing, while the health economic evidence to support testing of KRAS/NRAS mutational status and chemo/EGFR therapy choice was inconclusive, despite its widespread adoption in CRC treatment management. However, we also show that there is a paucity of high-quality cost-effectiveness studies to support clinical application of precision medicine approaches in CRC.

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