Circulating Tumour DNA as a Potential Cost-Effective Biomarker to Reduce Adjuvant Chemotherapy Overtreatment in Stage II Colorectal Cancer

Yat Hang To (), Koen Degeling, Suzanne Kosmider, Rachel Wong, Margaret Lee, Catherine Dunn, Grace Gard, Azim Jalali, Vanessa Wong, Maarten IJzerman, Peter Gibbs and Jeanne Tie
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Yat Hang To: Walter and Eliza Hall Institute
Koen Degeling: University of Melbourne
Suzanne Kosmider: Western Health
Rachel Wong: Walter and Eliza Hall Institute
Margaret Lee: Walter and Eliza Hall Institute
Catherine Dunn: Walter and Eliza Hall Institute
Grace Gard: Walter and Eliza Hall Institute
Azim Jalali: Walter and Eliza Hall Institute
Vanessa Wong: Walter and Eliza Hall Institute
Maarten IJzerman: University of Melbourne
Peter Gibbs: Walter and Eliza Hall Institute
Jeanne Tie: Walter and Eliza Hall Institute

PharmacoEconomics, 2021, vol. 39, issue 8, No 8, 953-964

Abstract: Abstract Background and Objective Substantial adjuvant chemotherapy (AC) overtreatment for stage II colorectal cancer results in a health and financial burden. Circulating tumour DNA (ctDNA) can improve patient selection for AC by detecting micro-metastatic disease. We estimated the health economic potential of ctDNA-guided AC for stage II colorectal cancer. Methods A cost-utility analysis was performed to compare ctDNA-guided AC to standard of care, where 22.6% of standard of care patients and all ctDNA-positive patients (8.7% of tested patients) received AC and all ctDNA-negative patients (91.3%) did not. A third preference-sensitive ctDNA strategy was included where 6.8% of ctDNA-negative patients would receive AC. A state-transition model was populated using data from a prospective cohort study and clinical registries. Health and economic outcomes were discounted at 5% over a lifetime horizon from a 2019 Australian payer perspective. Extensive scenario and probabilistic analyses quantified model uncertainty. Results Compared to standard of care, the ctDNA and preference-sensitive ctDNA strategies increased quality-adjusted life-years by 0.20 (95% confidence interval − 0.40 to 0.81) and 0.19 (− 0.40 to 0.78), and resulted in incremental costs of AUD − 4055 (− 16,853 to 8472) and AUD − 2284 (− 14,685 to 10,116), respectively. Circulating tumour DNA remained cost effective at a willingness to pay of AUD 20,000 per quality-adjusted life-year gained throughout most scenario analyses in which the proportion of ctDNA-positive patients cured by AC and compliance to a ctDNA-negative test results were decreased. Conclusions Circulating tumour-guided AC is a potentially cost-effective strategy towards reducing overtreatment in stage II colorectal cancer. Results from ongoing randomised clinical studies will be important to reduce uncertainty in the estimates.

Date: 2021
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DOI: 10.1007/s40273-021-01047-0

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