A Multigene Prognostic Assay for Selection of Adjuvant Chemotherapy in Patients with T3, Stage II Colon Cancer: Impact on Quality-Adjusted Life Expectancy and Costs

491 Background: Uncertainty exists regarding the use of adjuvant therapy in patients with stage II colon cancer. To assist decision making, we compared quality-adjusted life expectancy and costs associated with using a multigene recurrence score (RS) assay with the use of clinicopathological factors currently recommended in clinical guidelines. Methods: A state-transition (Markov) model was developed to assess outcomes associated with the use of the RS (Oncotype Dx gene expression assay) in adjuvant therapy decisions in stage II colon cancer (excluding T4 tumors and those with deficient DNA mismatch repair). RS test characteristics were based on results reported from a randomized controlled trial (QUASAR, Kerr et al. ASCO, 2009). Current rates of administering adjuvant chemotherapy (aCTX) as a function of age, lymphatic invasion, tumor stage, and number of lymph nodes examined was derived from the NCCN Colon/Rectum Cancer Outcomes study (Earle et al, J Surg Oncol, 2009). Effects of aCTX on recurrence risk were based on published data. Medicare fee schedules were used to estimate cost; toxicities, recurrence, and quality-of-life adjustments were obtained from published studies. Results: Treatment decisions based on RS and a patient's years of life remaining without cancer recurrence would reduce aCTX use by 17% compared with current treatment patterns, and increase quality-adjusted life expectancy by an average of 0.035 years. With lower use of aCTX, direct medical costs are expected to decrease by an average of $2,971 per patient. One-way sensitivity analysis predicts overall QALY improvement with the RS through a range of variables, with the results most sensitive to the disutility associated with aCTX use. Sensitivity analyses also show the assay to be cost-saving under a variety of conditions. Conclusions: Clinical use of a multigene RS to assess risk of recurrence in T3 stage II colon cancers with intact mismatch repair is likely to improve quality-adjusted life expectancy and be cost-saving from a societal perspective. Patient age and disutility associated with chemotherapy are important considerations in adjuvant treatment decisions. [Table: see text]

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

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284821995715 ◽

2021 ◽

Vol 14 ◽

pp. 175628482199571

Author(s):

Gabrielle Jongeneel ◽

Marjolein J. E. Greuter ◽

Felice N. van Erning ◽

Miriam Koopman ◽

Geraldine R. Vink ◽

...

Keyword(s):

Colon Cancer ◽

Cost Effectiveness ◽

Adjuvant Chemotherapy ◽

Stage Ii ◽

Dutch Guideline ◽

Selection Strategies ◽

Life Years ◽

Stage Ii Colon Cancer ◽

Perfect Adherence ◽

Selection Of

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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