BACKGROUND: Imatinib mesylate, an orally administered kinase inhibitor that 
targets the Kit (CD117) protein, currently has 10 approved indications including 
treatment of chronic myelogenous leukemia and metastatic gastrointestinal 
stromal tumors (GIST). Treatment with adjuvant imatinib following surgical 
resection of localized Kit-positive GIST, the most recent FDA-approved 
indication (December 2008), has been shown to significantly improve 
recurrence-free survival (RFS) compared with surgical resection alone. Although 
adjuvant imatinib has proven effective in clinical trials, it is important to 
consider the economic impact to health plans of introducing imatinib in 
accordance with its new labeled indication.
OBJECTIVE: To evaluate the budgetary impact over a 3-year time horizon of 
treating patients with localized Kit-positive GIST with 1 year of adjuvant 
imatinib following surgical resection.
METHODS: A Markov model was developed to predict patients' transitions across 
health states defined by initial treatment (surgical resection followed by 
adjuvant imatinib 400 milligrams [mg] daily versus surgical resection alone), 
recurrence, and progression. Treatments for a first recurrence were (a) imatinib 
400 mg daily for recurrences following resection only or after completion of 1 
year of treatment with imatinib 400 mg daily and (b) imatinib 800 mg daily for 
recurrence during active treatment with imatinib 400 mg daily. Treatments for 
further progression were imatinib 800 mg daily, sunitinib, or best supportive 
care (BSC) following imatinib 400 mg per day, and sunitinib or BSC following 
imatinib 800 mg daily. Recurrence rates were derived from the American College 
of Surgeons Oncology Group (ACOSOG) Z9001 clinical trial, which compared 1 year 
of adjuvant imatinib following surgical resection with surgical resection only. 
The total number of patients with localized and surgically resected GIST 
(incidence rate of 0.36 per 100,000) was estimated from epidemiologic studies of 
GIST. Uptake of treatment with imatinib was estimated from unpublished data from 
qualitative market research funded by the study sponsor. The uptake rate 
assumptions reflected both (a) the percentage of patients with Kitpositive 
disease and (b) the percentage of clinically eligible patients who would use 
imatinib. Costs were estimated by combining unit costs from published sources 
with expected resource utilization based on the clinical trial publication and 
National Comprehensive Cancer Network guidelines on the treatment of patients 
with GIST. To obtain estimates of the budgetary impact, we compared estimated 
health care costs with versus without adjuvant imatinib, where health care costs 
with imatinib reflected the costs of treatment minus cost offsets associated 
with delayed or avoided recurrence or progression. All "with" scenarios assumed 
no additional uses other than surgically resected localized Kit-positive GIST 
(i.e., no change in off-label use of imatinib). The budgetary impact was 
estimated for the first 3 years after the introduction of adjuvant imatinib in 
accordance with its new labeled indication in a hypothetical plan population of 
10 million persons. Results were calculated both as total budgetary impact and 
as per member per month (PMPM) cost in 2009 dollars. Sensitivity analyses were 
performed to test the robustness of model results to changes in parameter 
estimates.
RESULTS: The model predicted 36 incident resected GIST cases per year in a 
health plan of 10 million members. The estimated counts of cases treated with 
adjuvant imatinib were 10.8, 16.2, and 21.6 in the first, second, and third 
years after introduction, respectively, with the annual increases attributable 
to changes in the proportion of patients with resected GIST assumed to use 
imatinib (30% in year 1, rising to 45% in year 2 and 60% in year 3). The model 
predicted that treatment of these cases with imatinib will increase pharmacy 
costs by an additional $505,144 in the first year, $757,717 in the second year, 
and $1,010,289 in the third year. Increased resource use associated with 
monitoring patients during and after treatment with adjuvant imatinib would cost 
an additional $21,564, $38,145, and $56,605 in the first, second, and third 
years, respectively. Recurrence would be avoided or delayed in 7 patients over 
the 3-year period. Avoided or delayed recurrences would result in cost offsets 
of $61,583 in the first year, $156,702 in the second year, and $233,849 in the 
third year. The net budgetary impact was estimated to be $465,126 in the first 
year (less than $0.01 PMPM), $639,159 in the second year ($0.01 PMPM), and 
$833,044 in the third year ($0.01 PMPM). Results of sensitivity analyses 
indicated that the budgetary impact in the third year is most sensitive to 
changes in the price of adjuvant imatinib and recurrence rates.
CONCLUSIONS: The model predicted that the introduction of adjuvant imatinib for 
treatment of surgically resected, localized, Kit-positive GIST will lead to a 
net budgetary impact of $0.01 PMPM in the third year after introduction assuming 
change in use only in accordance with the new labeled indication. Approximately 
11.7%-21.9% of the cost of adjuvant imatinib is offset by the reduction in costs 
associated with GIST recurrence.