Abstract
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.
Highlights
Colorectal cancer (CRC) is the second most common cancer in women (~746,000 new cases annually), and third most common in men (~614,000 new cases annually); and the annual number of deaths approaches 700,000 [1]
Of the articles we identified, both the Canadian study by the Health Quality Ontario (HQO) [35] and the UK study by Westwood et al [38] generate incremental cost-effectiveness ratio (ICER) below the National Institute for Health and Care Excellence (NICE) threshold for KRAS WT guided therapy compared to best supportive care (BSC) and chemotherapy respectively
We disagree with the Frank and Mittendorf systematic review on the lack of evidence to make a decision on the cost-effectiveness of Uridine 5′-diphosphoglucuronosyltransferase family 1 member A1 gene (UGT1A1), because our analysis indicates that there is enough evidence to support the assertion that the use of UGT1A1 genotyping to reduce irinotecan dosing is not cost-effective
Summary
Colorectal cancer (CRC) is the second most common cancer in women (~746,000 new cases annually), and third most common in men (~614,000 new cases annually); and the annual number of deaths approaches 700,000 [1]. Within the UK, in 2015, www.oncotarget.com almost 42,000 new cases of CRC were documented [4], with over 16,000 CRC deaths [5] and a cost of €2.3 billion (Henderson et al Manuscript in Preparation). Identification of appropriate prognostic and predictive molecular biomarkers (MBMs), which can distinguish between these different subtypes, can assist clinical decisionmaking, such that patients receive the most appropriate treatment based on their molecular profile. This stratified or precision medicine approach has the potential to contribute to enhanced therapeutic efficacy, while minimising treatment-related toxicity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
