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

To, Yat Hang; Degeling, Koen; Kosmider, Suzanne; Wong, Rachel; Lee, Margaret; Dunn, Catherine; Gard, Grace; Jalali, Azim; Wong, Vanessa; IJzerman, Maarten J.; Gibbs, Peter; Tie, Jeanne

doi:10.1007/s40273-021-01047-0

Cited by 20 publications

(28 citation statements)

References 43 publications

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“…Notably, three of the studies demonstrated that a reduction in AC prescription (range: 14-22%) resulted in biomarker informed care dominating SOC, demonstrating the positive economic impact of reducing AC overtreatment. [48][49][50] The two remaining studies reported that compared to no AC, biomarker patient selection was cost-effectiveness but notably in this analysis, the uptake of AC in the biomarker strategy was limited (range: 5.8-7.4%). However, as a biomarker's impact depends on whether it actually can change treatment decisions, economic evaluations should model compliance to biomarker results but only two studies did so.…”

Section: Discussionmentioning

confidence: 94%

“…Assigning AC to patients with detectable ctDNA alone resulted in a 13% absolute reduction in AC prescription compared to SOC. 50 Furthermore, they considered a scenario in which some ctDNA negative patients would also receive AC. Both complete and incomplete adherence to ctDNA testing resulted in ctDNA dominating SOC.…”

Section: Oxaliplatin-based Acmentioning

confidence: 99%

“…Both complete and incomplete adherence to ctDNA testing resulted in ctDNA dominating SOC. 50 Jongeneel et al compared several AC selection strategies in stage II cancers that were T4, and MSS tumours utilising a biomarker approach based on the presence of BRAF and KRAS mutations. 51 The study concluded that AC prescription based on molecular biomarkers (4.8%) dominates no patients receiving AC.…”

Section: Oxaliplatin-based Acmentioning

confidence: 99%

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Health economic evidence for adjuvant chemotherapy in stage II and III colorectal cancer: a systematic review

Gibbs

Tie

et al. 2022

Preprint

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Objective: The aims of this study was to appraise the health economic evidence for adjuvant chemotherapy (AC) strategies in stage II and III colorectal cancer (CRC) and to identify gaps in the available evidence that might inform further research.Method : A systematic review of published economic evaluations was undertaken. Four databases were searched and full-text publications in English were screened for inclusion. A narrative synthesis was performed to summarise the evidence.Results: Thirty-eight studies were identified and stratified by cancer stage and AC strategy. The majority (89%) were full economic evaluations considering both health outcomes, usually measured as quality-adjusted life years (QALYs), and costs. AC was found to be cost-effective compared to no AC for both stage II and III CRC. Oral and oxaliplatin-based AC was cost-effective for stage III. Three months of CAPOX was cost-effective compared to 6-month in high-risk stage II and stage III CRC. Preliminary evidence suggests that biomarker approaches to AC selection in stage II can reduce costs and improve health outcomes. Notably, assessment of QALYs were predominantly reliant on a small number of non-contemporary health-utility studies. Only 32% of studies considered societal costs such as travel and time off work. Conclusions: Published economic evaluations consistently supported the use of AC in stage II and III colorectal cancer. Biomarker-driven approaches to patient selection have great potential to be cost-effective, but more robust clinical and economic evidence is warranted. Patient surveys embedded into clinical trials may address critical knowledge gaps regarding accurate assessment of QALYs and societal costs in the modern era.

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Section: Discussionmentioning

confidence: 94%

Section: Oxaliplatin-based Acmentioning

confidence: 99%

Section: Oxaliplatin-based Acmentioning

confidence: 99%

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Health economic evidence for adjuvant chemotherapy in stage II and III colorectal cancer: a systematic review

Gibbs

Tie

et al. 2022

Preprint

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“…The Immunotherapy treated group is known to have delayed treatment effects and/or a subgroup of patient who have better treatment response [56], [62]- [64]. The mixture cure time to event distribution (mixture cure model) have been proposed and used as a modelling solution to improve long-term projection in the immunotherapy treated subgroup [56]- [58], [65], [66]. We have shown that under the standard time to event distribution, the model results a lower long-term OS estimate compared to the realworld OS estimates.…”

Section: Discussionmentioning

confidence: 99%

“…Standard time to event distributions may fail to capture these differences and in turn under-estimate longterm survival outcome. To account for that, we have assumed that the time to event from start of rst-line immunotherapy (i.e., from L1T to L2T and to Death) follows a mixture cure time to event distribution [56]- [58]. The mixture cure time to event was implemented by assuming that 23 percent of patients were long-term survivors (we referred to the cured fraction as long-term survivor fraction).…”

Section: Simulating Time To Event For Immunotherapymentioning

confidence: 99%

Modelling of Lung Cancer Therapy; Modelled And Real-World Impact of Targeted Therapy And Immunotherapy In The Netherlands

Mfumbilwa

Wilschut

Simons

et al. 2022

Preprint

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Recent discoveries in molecular diagnostics and lung cancer drugs have improved the treatment of patients with advanced (inoperable) non-squamous NSCLC from solely platinum based chemotherapy to more personalized treatment including targeted therapies and immunotherapies. However, these improvements come at considerable costs, highlighting the need to assess cost-effectiveness for optimization of lung cancer care. Traditionally, cost-effectiveness models built to evaluate new lung cancer treatments were based on randomized control trial (RCT) findings. The strict RCT inclusion criteria make RCT patients not representative of real-world patients: Patients in RCT have better prognosis compared to real-world patients. Therefore, in this study we have developed and validated a diagnosis-treatment decision model for patients with advanced (inoperable) non-squamous NSCLC based on real-world data in the Netherlands. The model is a patient-level microsimulation model implemented as discrete event simulation with five health events. Patients are simulated from diagnosis to death, including at most three treatment lines. The base-model (non-personalized strategy) was populated using real-world data of patients treated with platinum-based chemotherapy between 2008 – 2014 in one of six Dutch’s teaching hospitals. To allow simulation of personalized care, molecular tumor characteristics were incorporated in the model based on the literature. The impact of novel targeted treatments and immunotherapies was included based on published RCTs. To validate the model, we compared survival under a personalized treatment strategy against observed real-world survival. This model can be used for health-care evaluation of personalized treatment for patients with advanced (inoperable) NSCLC in the Netherlands.

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Budget Impact Analysis of Circulating Tumor DNA Testing for Colon Cancer in Commercial Health and Medicare Advantage Plans

Li,

Heer,

Sloane

et al. 2024

JAMA Health Forum

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ImportanceIn a randomized clinical trial, treatment guided by tumor-informed circulating tumor (ct)DNA testing reduced adjuvant chemotherapy use without compromising recurrence-free survival in patients with stage II colon cancer. The potential effects of adopting ctDNA testing into routine patient care is unknown.ObjectiveTo compare the total cost of patient care scenarios with and without the adoption of ctDNA testing.Design, Setting, and ParticipantsThis budget impact analysis was conducted from the perspectives of US commercial health and Medicare Advantage payers. A decision-analytical model was populated with age-specific incidence of colon cancer, use of adjuvant chemotherapy, and use of single-agent or multiagent regimens. Total cost was estimated with the costs of ctDNA testing, drug acquisition, administration, surveillance, and adverse events. The analysis was conducted from September 2023 to January 2024.ExposuresThe adoption of ctDNA testing.Main Outcomes and MeasuresThe incremental cost in the first year following the adoption of ctDNA testing, where testing will affect patient treatment and costs.ResultsIn hypothetical plans with 1 million individuals covered, 35 commercial health plan members and 102 Medicare Advantage members aged 75 years and younger were eligible for ctDNA testing. In the base case with a 50% adoption rate, total cost savings were $221 684 (equivalent to $0.02 per member per month [PMPM]) for a commercial payer and $116 720 (equivalent to $0.01 PMPM) for a Medicare Advantage payer. Cost savings were robust to variations in assumptions of all parameters in the commercial population but sensitive to variations in assumptions of adjuvant chemotherapy use rates in the Medicare Advantage population. The number needed to test to avoid 1 patient receiving adjuvant chemotherapy was 4 in the commercial population and 10 in the Medicare Advantage population. The budget-neutral cost for ctDNA testing was $16 202 for a commercial payer and $5793 for a Medicare Advantage payer.Conclusions and RelevanceUse of tumor-informed ctDNA testing to guide adjuvant chemotherapy in postsurgery patients with stage II colon cancer was projected to result in cost savings for both commercial and Medicare Advantage payers. Adoption of ctDNA testing is therefore advantageous from a budgetary perspective.

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

Cited by 20 publications

References 43 publications

Health economic evidence for adjuvant chemotherapy in stage II and III colorectal cancer: a systematic review

Health economic evidence for adjuvant chemotherapy in stage II and III colorectal cancer: a systematic review

Modelling of Lung Cancer Therapy; Modelled And Real-World Impact of Targeted Therapy And Immunotherapy In The Netherlands

Budget Impact Analysis of Circulating Tumor DNA Testing for Colon Cancer in Commercial Health and Medicare Advantage Plans

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