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

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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.

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Acknowledgements

The authors acknowledge BioGrid Australia for providing data access and support to the ACCORD and TRACC databases.

Author information

Authors and Affiliations

  1. Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia

    Yat Hang To, Rachel Wong, Margaret Lee, Catherine Dunn, Grace Gard, Azim Jalali, Vanessa Wong, Peter Gibbs & Jeanne Tie

  2. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Yat Hang To, Catherine Dunn & Jeanne Tie

  3. Cancer Health Services Research, Centre for Cancer, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia

    Koen Degeling & Maarten IJzerman

  4. Cancer Health Services Research, Centre for Health Policy, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia

    Koen Degeling & Maarten IJzerman

  5. Department of Medical Oncology, Western Health, Melbourne, VIC, Australia

    Suzanne Kosmider, Margaret Lee, Grace Gard, Azim Jalali, Peter Gibbs & Jeanne Tie

  6. Department of Medical Oncology, Eastern Health, Melbourne, VIC, Australia

    Rachel Wong & Margaret Lee

  7. Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, VIC, Australia

    Rachel Wong & Margaret Lee

  8. Department of Medical Oncology, LaTrobe Regional Hospital, Traralgon, VIC, Australia

    Azim Jalali

  9. Department of Medical Oncology, Ballarat Health, Ballarat, VIC, Australia

    Vanessa Wong

  10. Department of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Maarten IJzerman

  11. Faculty of Medicine and Health Sciences, University of Melbourne, Melbourne, VIC, Australia

    Peter Gibbs & Jeanne Tie

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  1. Yat Hang To
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Corresponding author

Correspondence to Yat Hang To.

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Funding

No funding was received for the conduct of this study or the preparation of this article. Roche Product Pty Limited (Australia) provided financial assistance for the development, installation and maintenance of the TRACC database, data from which were used in this analysis.

Conflicts of interest/Competing interests

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 have no conflicts of interests that are directly relevant to the content of this article.

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Availability of data and material

The data generated during and/or analysed during the current study are available from the corresponding author, upon reasonable request.

Code availability

The custom codes generated for this study are available from the corresponding author, upon reasonable request.

Author contributions

YHT, KD and JT contributed to the study conception and design. Material preparation, data collection and analysis were performed by YHT under supervision of KD. Further supervision was provided by JT. All authors contributed to the interpretation and discussion of the results. The initial draft of the manuscript was written by YHT in collaboration with KD, and critically reviewed by all other authors. All authors read and approved the final manuscript.

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To, Y.H., Degeling, K., Kosmider, S. et al. Circulating Tumour DNA as a Potential Cost-Effective Biomarker to Reduce Adjuvant Chemotherapy Overtreatment in Stage II Colorectal Cancer. PharmacoEconomics 39, 953–964 (2021). https://doi.org/10.1007/s40273-021-01047-0

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