The cost-utility of adjuvant chemotherapy using docetaxel and cyclophosphamide compared with doxorubicin and cyclophosphamide in breast cancer

Abstract

Purpose: The adoption of a chemotherapeutic regimen in oncologic practice is a function of both its clinical and its economic impacts on cancer management. For breast cancer, U.S. Oncology trial 9735 reported significant improvements in disease-free and overall survival favoring adjuvant tc (docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks for 4 cycles) compared with ac (doxorubicin 60 mg/ m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks for 4 cycles). We carried out an economic evaluation to examine the cost-utility of adjuvant tc relative to ac, in terms of cost per quality-adjusted life year (qaly) gained, given the improved breast cancer outcomes and higher costs associated with the tc regimen.

Methods: A Markov model was developed to calculate the cumulative costs and qalys gained over a 10-year horizon for hypothetical cohorts of women with breast cancer treated with ac or with tc. Event rates, costs, and utilities were derived from the literature and local resources. Efficacy and adverse events were based on results reported from U.S. Oncology trial 9735. The model takes a third-party direct payer perspective and reports its results in 2008 Canadian dollars. Costs and benefits were both discounted at 3%.

Results: At a 10-year horizon, tc was associated with $3,960 incremental costs and a 0.24 qaly gain compared with ac, for a favorable cost-utility of $16,753 per qaly gained. Results were robust to model assumptions and input parameters.

Conclusions: Relative to ac, tc is a cost-effective adjuvant chemotherapy regimen, with a cost-effectiveness ratio well below commonly applied thresholds.

Keywords: Breast cancer; ac chemotherapy, cost; adjuvant therapy; chemotherapy; tc chemotherapy; utility analysis.

FIGURE 1

Model schema. Health states incorporated into the model are shown in circles, and possible transitions between health states are depicted by arrows. All patients enter the model in the Chemotherapy state (docetaxel–cyclophosphamide or doxorubicin–cyclophosphamide) and move to Disease-Free state after completion of chemotherapy treatment. Chemotherapy-related adverse events could occur during Chemotherapy state [that is, chemotherapy-induced nausea and vomiting (cinv) or febrile neutropenia (fn)] or after transition to Disease-Free state [that is, acute myeloid leukemia (aml) or myelodysplasia (mds), or congestive heart failure (chf)]. Patients in Disease-Free state could develop Local Relapse or Distant Relapse. Death might occur with or without relapse or as a result of chemotherapy adverse events.

FIGURE 2

Sensitivity analysis. The y axis shows the parameters and the ranges tested in the sensitivity analysis; the x axis reflects the resulting cost–utility value in thousands of Canadian dollars per quality-adjusted life year (qaly) gained. The dashed vertical line represents the mean cost–utility result (CA$16,753/qaly gained), and each bar shows the range of the cost–utility estimate for each parameter tested. For each parameter tested, the lower and higher cost–utility values in the bar respectively reflect the cost–utility estimates for the first and second columns of the range rested. The order of variables from top to bottom, with corresponding longer-to-shorter bars in the tornado plot, reflects the variables with more-to-less impact on the cost–utility results. tc = docetaxel–cyclophosphamide; ac = doxorubicin–cyclophosphamide; aml/mds = acute myeloid leukemia or myelodysplastic syndrome; chf = congestive heart failure; cinv = chemotherapy-induced nausea and vomiting. Parameter Baseline Range tested

FIGURE 3

Cost-effectiveness by analysis horizon. The y axis shows the cost per quality-adjusted life year (qaly) gained in Canadian dollars; the x axis shows the analysis horizon. The graph shows cost per qaly gained as a function of the time horizon from adjuvant chemotherapy treatment.

FIGURE 4

Cost-effectiveness acceptability curve. The x axis shows willingness-to-pay per quality-adjusted life year (qaly) gained in Canadian dollars; the y axis shows the probability that docetaxel– cyclophosphamide (tc) is cost-effective. The likelihood that tc is cost-effective is shown at various thresholds of willingness-to-pay per qaly gained; the probabilities are, respectively, 91% and 97% that tc is cost-effective at the commonly applied thresholds of $50,000 and $100,000 per qaly gained.