Model-based effectiveness and cost-effectiveness of risk-based selection strategies for adjuvant chemotherapy in Dutch stage II colon cancer patients

Background: We aimed to evaluate the cost-effectiveness of risk-based strategies to improve the selection of surgically treated stage II colon cancer (CC) patients for adjuvant chemotherapy. Methods: Using the ‘Personalized Adjuvant TreaTment in EaRly stage coloN cancer’ (PATTERN) model, we evaluated five selection strategies: (1) no chemotherapy, (2) Dutch guideline recommendations assuming observed adherence, (3) Dutch guideline recommendations assuming perfect adherence, (4) biomarker mutation OR pT4 stage strategy in which patients with MSS status combined with a pT4 stage or a mutation in BRAF and/or KRAS receive chemotherapy assuming perfect adherence and (5) biomarker mutation AND pT4 stage strategy in which patients with MSS status combined with a pT4 stage tumor and a BRAF and/or KRAS mutation receive chemotherapy assuming perfect adherence. Outcomes were number of CC deaths per 1000 patients and total discounted costs and quality-adjusted life-years (QALYs) per patient (pp). Analyses were conducted from a societal perspective. The robustness of model predictions was assessed in sensitivity analyses. Results: The reference strategy, that is, no adjuvant chemotherapy, resulted in 139 CC deaths in a cohort of 1000 patients, 8.077 QALYs pp and total costs of €22,032 pp. Strategies 2–5 were more effective (range 8.094–8.217 QALYs pp and range 118–136 CC deaths per 1000 patients) and more costly (range €22,404–€25,102 pp). Given a threshold of €50,000/QALY, the optimal use of resources would be to treat patients with either the full adherence strategy and biomarker mutation OR pT4 stage strategy. Conclusion: Selection of stage II CC patients for chemotherapy can be improved by either including biomarker status in the selection strategy or by improving adherence to the Dutch guideline recommendations.

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Model-based evaluation of the cost effectiveness of 3 versus 6 months’ adjuvant chemotherapy in high-risk stage II colon cancer patients

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284820954114 ◽

2020 ◽

Vol 13 ◽

pp. 175628482095411

Author(s):

Gabrielle Jongeneel ◽

Marjolein J. E. Greuter ◽

Felice N. van Erning ◽

Miriam Koopman ◽

Geraldine R. Vink ◽

...

Keyword(s):

Colon Cancer ◽

Cost Effectiveness ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Treatment Duration ◽

Standard Of Care ◽

Stage Ii ◽

Life Years ◽

Stage Ii Colon Cancer ◽

The Cost

Background: Our aim was to evaluate the cost effectiveness of 3 months’ adjuvant chemotherapy versus 6 months in high-risk (T4 stage + microsatellite stable) stage II colon cancer (CC) patients. Methods: Using the validated PATTERN Markov cohort model, which simulates the disease progression of stage II CC patients from diagnosis to death, we first evaluated a reference strategy in which high-risk patients were treated with chemotherapy for 6 months. In the second strategy, treatment duration was shortened to 3 months. Both strategies were evaluated for CAPOX (capecitabine plus oxaliplatin) and FOLFOX (fluorouracil, leucovorin and oxaliplatin). Based on trial data, we assumed that shortened treatment duration compared with a 6-month regimen was equally effective for CAPOX and less effective for FOLFOX. Adverse events were highest in the 6-month strategy. Analyses were conducted from a societal perspective using a lifelong time horizon. Outcomes were number of CC deaths per 1000 patients and total discounted costs and quality-adjusted life-years (QALYs) per patient (pp). Incremental net monetary benefit (iNMB) was calculated using a willingness-to-pay value of €50,000/QALY. Results: For CAPOX, the 6-month strategy resulted in 316 CC deaths per 1000 patients, 6.71 QALYs pp and total costs of €41,257 pp. The 3-month strategy resulted in an equal number of CC deaths, but higher QALYs (6.80 pp) and lower costs (€37,645 pp), leading to a iNMB of €8454 per person for 3 months versus 6 months. For FOLFOX, the 6-month strategy resulted in 316 CC deaths per 1000 patients, 6.71 QALYs pp and total costs of €47,135 pp. The 3-month strategy resulted in more CC deaths (393), lower QALYs (6.19 pp) and lower costs (€44,389 pp). An iNMB of −€23,189 was found for 3 months versus 6 months. Conclusion: Our findings indicate that 3 months’ adjuvant chemotherapy should be considered as standard of care in high-risk stage II CC patients for CAPOX, but not for FOLFOX.

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Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Stage II Colon Cancer (DYNAMIC Trial): Statistical Analysis Plan

10.1101/2021.09.02.21262816 ◽

2021 ◽

Author(s):

Jeanne Tie ◽

Serigne N. Lo ◽

Joshua D. Cohen ◽

Yuxuan Wang ◽

Rachel Wong ◽

...

Keyword(s):

Colon Cancer ◽

Data Analysis ◽

Statistical Analysis ◽

Adjuvant Chemotherapy ◽

Statistical Analysis Plan ◽

Stage Ii ◽

Sensitivity Analyses ◽

Life Years ◽

Stage Ii Colon Cancer ◽

Circulating Tumour Dna

ABSTRACTBackgroundDetection of circulating tumour DNA (ctDNA) after curative intent treatment reflects the presence of minimal residual disease and predicts for recurrence. DYNAMIC trial is a randomised phase II investigating the clinical utility of ctDNA-guided adjuvant treatment strategy compared with the standard of care (non-ctDNA based) approach in patients with stage II colon cancer. The primary trial endpoint is recurrence-free survival estimated from Kaplan Meier Method at 2 years. Secondary endpoints include proportion of patients treated with adjuvant chemotherapy, time-to-recurrence, overall survival, ctDNA clearance rate (investigational arm) and quality-adjusted life-years.ObjectiveTo outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis.MethodsThe SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data.Trial RegistrationANZ Clinical Trials Registry, ACTRN12615000381583. Registered on 27th April 2015.

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Early cost-effectiveness analysis of risk-based selection strategies for adjuvant treatment in stage II colon cancer: the potential value of prognostic molecular markers

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-21-0078 ◽

2021 ◽

pp. cebp.0078.2021

Author(s):

Gabrielle Jongeneel ◽

Marjolein JE Greuter ◽

Natalia Kunst ◽

Felice N van Erning ◽

Miriam Koopman ◽

...

Keyword(s):

Colon Cancer ◽

Molecular Markers ◽

Cost Effectiveness ◽

Adjuvant Treatment ◽

Cost Effectiveness Analysis ◽

Stage Ii ◽

Potential Value ◽

Selection Strategies ◽

Effectiveness Analysis ◽

Stage Ii Colon Cancer

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Cost-effectiveness of adjuvant therapy for treatment of stage II colon cancer in patients with diabetes.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.421 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 421-421

Author(s):

T. Dinh ◽

P. Alperin ◽

B. H. O'Neil

Keyword(s):

Colon Cancer ◽

Cost Effectiveness ◽

Side Effects ◽

Adjuvant Chemotherapy ◽

Adjuvant Therapy ◽

Cancer Patients ◽

Stage Ii ◽

Diabetic Patients ◽

Response To Chemotherapy ◽

Stage Ii Colon Cancer

421 Background: The decision to treat stage II colon cancer patients with adjuvant chemotherapy involves assessment of life expectancy, risk for recurrent disease, and the potential benefit and likelihood of adverse effects from treatment. This is a challenging task, particularly for patients with pre-existing chronic illnesses such as diabetes, which may increase side effects and potentially lessen response to chemotherapy. Methods: We use the Archimedes Model to analyze cost effectiveness of adjuvant therapy in stage II colon cancer patients with pre-existing diabetes. The Archimedes Model is a large-scale, integrated mathematical model of human physiology, diseases, and healthcare systems, including pathways relating to diabetes, cardiovascular disease, and cancers of the breast, lung, and colon. The colon cancer model is built using the SEER, ACCENT databases and meta-analyses of clinical trials. Costs relating to colon cancer, diabetes and its complications are based on Medicare reimbursement rates. We simulate a trial in which stage II colon cancer patients are subjected to two treatment strategies: no treatment vs. adjuvant chemotherapy by FOLFOX regimen. We report incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life year (QALY) gained, of adjuvant therapy compared with no treatment. Results: Cost effectiveness is strongly dependent on a patient's tumor profile, age and duration of diabetes. For instance, adjuvant therapy saves ∼0.2 QALYs per person in stage IIA patients who are 75 and older and have been diagnosed with diabetes >10 years, at an ICER of >$150,000/QALY gained. In contrast, it saves 1.1 QALYs per person in stage IIB patients aged 60-65, recently diagnosed with diabetes, at an ICER of <$30,000/QALY gained. Results are sensitive to assumptions on efficacy and side effects of chemotherapy in diabetic patients, as well as cost of adjuvant therapy. Conclusions: The current study suggests that the decision to proceed with adjuvant chemotherapy requires careful assessment of severity of diabetes in stage II colon cancer patients with pre-existing diabetes. No significant financial relationships to disclose.

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