Cost-Effectiveness Analysis of Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumor: A Systematic Review.

Background: The introduction of tyrosine kinase inhibitor (TKI) therapy has dramatically improved the clinical effectiveness of patients with locally advanced and/or metastatic gastrointestinal stromal tumors (GIST), and this systematic review was conducted aiming at the cost-effectiveness analysis of TKIs in GIST. Methods: A thorough literature search of online databases was performed, using appropriate terms such as "gastrointestinal stromal tumor or GIST," "cost-effectiveness," and "economic evaluation." Data extraction was conducted independently by two authors, and completeness of reporting and quality of the evaluation were assessed. The systematic review was conducted following the PRISMA statement. Results: Published between 2005 and 2020, 15 articles were incorporated into the systematic review. For advanced GIST, imatinib followed by sunitinib was considered cost-effective, and regorafenib was cost-effective compared with imatinib re-challenge therapy in the third-line treatment. For resectable GIST, 3-year adjuvant imatinib therapy represented a cost-effective treatment option. The precision medicine-assisted imatinib treatment was cost-effective compared with empirical treatment. Conclusion: Although identified studies varied in predicted costs and quality-adjusted life years, there was general agreement in study conclusions. More cost-effectiveness analysis should be conducted regarding more TKIs that have been approved for the treatment of GIST. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO: CRD42021225253.

Cost-effectiveness Analysis of Genetic Testing and Tailored First-Line Therapy for Patients With Metastatic Gastrointestinal Stromal Tumors.

Importance: Gastrointestinal stromal tumor (GIST) is frequently driven by oncogenic KIT variations. Imatinib targeting of KIT marked a new era in GIST treatment and ushered in precision oncological treatment for all solid malignant neoplasms. However, studies on the molecular biological traits of GIST have found that tumors respond differentially to imatinib dosage based on the KIT exon with variation. Despite this knowledge, few patients undergo genetic testing at diagnosis, and empirical imatinib therapy remains routine. Barriers to genetic profiling include concerns about the cost and utility of testing. Objective: To determine whether targeted gene testing (TGT) is a cost-effective diagnostic for patients with metastatic GIST from the US payer perspective. Design, Setting, and Participants: This economic evaluation developed a Markov model to compare the cost-effectiveness of TGT and tailored first-line therapy compared with empirical imatinib therapy among patients with a new diagnosis of metastatic GIST. The main health outcome, quality-adjusted life years (QALYs), and costs were obtained from the literature, and transitional probabilities were modeled from disease progression and survival estimates from randomized clinical trials of patients with metastatic GIST. Data analyses were conducted October 2019 to January 2020. Exposure: TGT and tailored first-line therapy. Main Outcomes and Measures: The primary outcome was QALYs and cost. Cost-effectiveness was defined using an incremental cost-effectiveness ratio, with an incremental cost-effectiveness ratio less than $100 000/QALY considered cost-effective. One-way and probabilistic sensitivity analyses were conducted to assess model stability. Results: Therapy directed by TGT was associated with an increase of 0.10 QALYs at a cost of $9513 compared with the empirical imatinib approach, leading to an incremental cost-effectiveness ratio of $92 100. These findings were sensitive to the costs of TGT, drugs, and health utility model inputs. Therapy directed by TGT remained cost-effective for genetic testing costs up to $3730. Probabilistic sensitivity analysis found that TGT-directed therapy was considered cost-effective 70% of the time. Conclusions and Relevance: These findings suggest that using genetic testing to match treatment of KIT variations to imatinib dosing is a cost-effective approach compared with empirical imatinib.

[Real world study and its application in gastrointestinal stromal tumor].

Gastrointestinal stromal tumor (GIST) is a relatively rare type of gastrointestinal tract tumors. Thus, it is difficult to perform randomized controlled trials (RCTs) of GIST in a single center, which are often plagued by a small number of participants. Real world study (RWS) is a complement to the evidence derived from traditional RCT. Emerging sources of real world data offer enormous opportunity for deeper understanding of why treatments work (or not) and for whom. Evidence generated from RWD can help clarify best use of treatments for individuals and populations, and care value. Thus, RWS of GIST has attracted much attention. RWS helps us better understand the diagnosis, treatment, prognosis and outcome prediction of GIST in clinical practice. GIST is often misdiagnosed as other tumor. A diagnostic test provides evidence on how well a test correctly identifies or rules out GIST. Therapeutic research aims to evaluate the effectiveness and/or safety of a therapy for GIST. Prognostic research aims to forecast the likely outcome of GIST, explore the factors affecting the outcome, and analyze quality of life. Predictive research aims to quantify the probability of identification or health outcome of GIST based on a set of predictors. Pharmacoeconomic data in real world can evaluate the cost-effectiveness of medicinal products for GISTs and serve as a guidance tool for optimal healthcare resource allocation. Attaching importance to data sourse and data quality, strenthening communicate with a qualified statistician, and the implementation of a standardized process are necessary for performing a high-quality RWS.

Optimizing the dose in patients treated with imatinib as first line treatment for gastrointestinal stromal tumours: A cost-effectiveness study.

AIMS: Patients with metastatic gastrointestinal stromal tumours (GIST) are treated in first line with the oral tyrosine kinase inhibitor, imatinib, until progressive disease. With this fixed dosing regimen, only approximately 40% of patients reach adequate plasma levels within the therapeutic index. Therapeutic drug monitoring (TDM) is a solution to reach plasma levels within the therapeutic index. However, introducing TDM will also increase costs, due to prolonged imatinib use and laboratory costs. The aim of this study was to evaluate the cost-effectiveness of TDM in patients with metastatic/unresectable GIST treated with imatinib as a first line treatment, compared with fixed dosing. METHODS: A survival model was created to simulate progression, mortality and treatment costs over a 5-year time horizon, comparing fixed dosing vs TDM-guided dosing. The outcomes measured were treatments costs, life-years and quality-adjusted life-years. RESULTS: Total costs over the 5-year time horizon were estimated to be €106 994.85 and €150 477.08 for fixed dosing vs TDM-guided dosing, respectively. A quality-adjusted life year gain of 0.74 (95% confidence interval 0.66-0.90) was estimated with TDM-guided dosing compared to fixed dosing. An average incremental cost-effectiveness ratio of €58 785.70 per quality-adjusted life year gained was found, mainly caused by longer use and higher dosages of imatinib. CONCLUSION: Based on the currently available data, this analysis suggests that TDM-guided dosing may be a cost-effective intervention for patients with metastatic/unresectable GIST treated with imatinib which will be improved when imatinib losses its patency.

The cost-saving effect of centralized histological reviews with soft tissue and visceral sarcomas, GIST, and desmoid tumors: The experiences of the pathologists of the French Sarcoma Group.

OBJECTIVE: This study examined the types of discordance occurring in the diagnosis of soft tissue and visceral sarcomas, gastrointestinal stromal tumors (GIST), and desmoid tumors, as well as the economic impact of diagnostic discrepancies. METHODS: We carried out a retrospective, multicenter analysis using prospectively implemented databases performed on a cohort of patients within the French RRePS network in 2010. Diagnoses were deemed to be discordant based on the 2013 World Health Organization (WHO) classification. Predictive factors of discordant diagnoses were explored. A decision tree was used to assess the expected costs of two strategies of disease management: one based on revised diagnoses after centralized histological review (option 1), the other on diagnoses without centralized review (option 2). Both were defined based on the patient and the disease characteristics, according to national or international guidelines. The time horizon was 12 months and the perspective of the French National Health Insurance (NHI) was retained. Costs were expressed in Euros for 2013. Sensitivity analyses were performed using low and high scenarios that included ± 20% estimates for cost. RESULTS: A total of 2,425 patients were included. Three hundred forty-one patients (14%) had received discordant diagnoses. These discordances were determined to mainly be benign tumors diagnosed as sarcomas (n = 124), or non-sarcoma malignant tumors diagnosed as sarcomas (n = 77). The probability of discordance was higher for a final diagnosis of desmoid tumors when compared to liposarcomas (odds ratio = 5.1; 95%CI [2.6-10.4]). The expected costs per patient for the base-case analysis (low- and high-case scenarios) amounted to €8,791 (€7,033 and €10,549, respectively) for option 1 and €8,904 (€7,057 and €10,750, respectively) for option 2. CONCLUSIONS: Our findings highlight misdiagnoses of sarcomas, which were found to most often be confused with benign tumors. Centralized histological reviews are likely to provide cost-savings for the French NHI.

Robotic Versus Laparoscopic Gastric Resection for Primary Gastrointestinal Stromal Tumors >5 cm: A Size-Matched and Location-Matched Comparison.

This study compared robotic (RR) and laparoscopic resection (LR) for primary gastrointestinal stromal tumors (GISTs) of the stomach >5 cm. Twelve consecutive patients who underwent RR from 2012 to 2015 were matched for tumor size and location with 24 patients who underwent LR from 2000 to 2012. The median tumor size was 7.1 cm (range, 5.5 to 11.5). GISTs were resected by wedge resection (91.7%) or distal gastrectomy. The median RR operative time was longer than that of LR (162.5 vs. 130 min, respectively; P=0.004). Only 1 LR patient required conversion. The time to flatus and hospital stay were similar between groups. Overall, 3 patients developed minor postoperative complications that were medically treated. Mortality was nil. All resections were R0. No difference was observed in the incidence of recurrence. RR was significantly more expensive (+21.6%) than LR. RR appears to be safe and feasible for GISTs>5 cm, but is associated with longer operative times and greater costs.

Overcoming Cost Implications of Mutational Analysis in Patients with Gastrointestinal Stromal Tumors: A Pragmatic Approach.

BACKGROUND: Genetic analysis of tissue derived from patients with advanced gastrointestinal stromal tumors (GISTs) is not uniformly applied on a national and international level, even though mutational data can provide clinically relevant prognostic and predictive information, especially in patients qualifying for treatment with expensive targeted agents. METHODS: The current article describes the rationale for genetic testing of GIST tissue, looks at financial implications associated with such analysis and speculates on potential cost savings introduced by routine mutational testing and tailored use of tyrosine kinase inhibitors based on genotyping. This work is based on a hypothetical analysis of epidemiological data, drug costs, reimbursement criteria and market research figures. RESULTS: The cost burden for routine genotyping of important genes in GISTs, especially in patients at high risk for relapse after primary surgery and in advanced, inoperable metastatic disease, is relatively low. The early identification of GISTs with primary resistance mutations should be the basis for personalized GIST treatment and reimbursement of drugs. As illustrated by Belgian figures, the exclusive use of a drug such as imatinib in patients who are likely to benefit from the agent based on genetic information can lead to significant cost savings, which outweigh the costs for testing. CONCLUSIONS: Mutational analysis of GIST should be considered early in all patients at risk for relapse after curative surgery and in the case of advanced, inoperable, metastatic disease. The costs for the actual genotyping should not be used as an argument against profiling of the tumor. The adjuvant and palliative systemic treatment of GISTs should be personalized based on the genotype and other known prognostic and predictive factors. Reimbursement criteria for essential agents such as imatinib should be adapted accordingly.

Laparoscopic versus open gastric wedge resection for primary gastrointestinal tumors: clinical outcomes and health care costs analysis.

The study aimed to compare laparoscopic wedge resection (LWR) versus open-wedge resections (OWR) for primary gastrointestinal stromal tumors (GISTs) of the stomach. Twenty-five patients who underwent LWR were matched by tumor size and location with 25 patients who underwent OWR. GISTs close to the pylorus or the esophagogastric junction, incidental, and metastatic GISTs were excluded. Demographic, clinical, and histologic variables did not differ between groups. Estimated blood loss, time to flatus, and duration of hospitalization were significantly lower in the LWR group. Overall, 6 patients developed minor postoperative complications that were medically treated. Mortality was nil. No group difference was observed for the incidence of diseases during the follow-up (average, 46.8 mo). The OWR procedure had significantly higher costs (+34%) than the LWR. Both techniques appear safe and oncologically feasible. However, laparoscopy is associated with faster recovery and shorter hospital stay, which reflect advantages in terms of contracted costs for the health care system.

The economic burden of gastrointestinal stromal tumor (GIST) recurrence in patients who have received adjuvant imatinib therapy.

OBJECTIVE: To estimate the economic burden of gastrointestinal stromal tumor (GIST) recurrence in patients who received imatinib adjuvant therapy. METHODS: Data from the MarketScan and PharmMetrics databases between January 2000 and March 2013 were extracted. Patients who had received at least one diagnosis of GIST, had undergone a primary surgery for GIST, and had received at least one prescription for imatinib were included in the analysis. An algorithm was applied to identify those who had a subsequent GIST recurrence. Patients who experienced a recurrence and those who did not have a recurrence were compared for differences in healthcare utilization measures and healthcare costs within 6 months after the recurrence, while adjusting for potential confounding factors. RESULTS: A total of 540 patients with primary resectable GIST who received imatinib adjuvant therapy were identified, including 444 (82.2%) patients who did not experience GIST recurrence and 96 (17.8%) patients who did experience recurrence. Patients who experienced GIST recurrence utilized significantly more healthcare resources in all categories than patients who did not have a recurrence, including the number of hospitalizations, days of hospitalization, emergency room visits, outpatient visits, and other medical services (all p-values <0.01). The total healthcare cost was significantly higher for patients with GIST recurrence, with a difference of $4464 per patient per month (p < 0.01). Both the medical and pharmacy costs were significantly higher with adjusted differences of $3488 and $1423 per patient per month, respectively (both p-values <0.01). CONCLUSIONS: Patients who had GIST recurrence after surgical resection incurred significantly more healthcare resource utilization and greater healthcare costs within 6 months after the recurrence than patients who did not have recurrence. These findings suggest that GIST recurrence is associated with a substantial economic burden.

The timing and probability of treatment switch under cost uncertainty: an application to patients with gastrointestinal stromal tumor.

BACKGROUND: Cost fluctuations render the outcome of any treatment switch uncertain, so that decision makers might have to wait for more information before optimally switching treatments, especially when the incremental cost per quality-adjusted life year (QALY) gained cannot be fully recovered later on. OBJECTIVE: To analyze the timing of treatment switch under cost uncertainty. METHODS: A dynamic stochastic model for the optimal timing of a treatment switch is developed and applied to a problem in medical decision taking, i.e. to patients with unresectable gastrointestinal stromal tumour (GIST). RESULTS: The theoretical model suggests that cost uncertainty reduces expected net benefit. In addition, cost volatility discourages switching treatments. The stochastic model also illustrates that as technologies become less cost competitive, the cost uncertainty becomes more dominant. With limited substitutability, higher quality of technologies will increase the demand for those technologies disregarding the cost uncertainty. The results of the empirical application suggest that the first-line treatment may be the better choice when considering lifetime welfare. CONCLUSIONS: Under uncertainty and irreversibility, low-risk patients must begin the second-line treatment as soon as possible, which is precisely when the second-line treatment is least valuable. As the costs of reversing current treatment impacts fall, it becomes more feasible to provide the option-preserving treatment to these low-risk individuals later on.

The economic impact of cytoreductive surgery and tyrosine kinase inhibitor therapy in the treatment of advanced gastrointestinal stromal tumours: a Markov chain decision analysis.

PURPOSE: The current first-line treatment for patients with recurrent or metastatic gastrointestinal stromal tumours (GIST) is management with tyrosine kinase inhibition (TKI). There is an undefined role for surgery in the management of these patients. This study uses a cost analysis to examine the economic impact of treating patients with TKI in combination with surgery at different time-points in their treatment trajectories. METHODS: A Markov chain decision analysis was modelled over a 2-year time horizon to determine costs associated with surgery in combination with imatinib mesylate (IM) or sunitinib malate (SU) in seven scenarios varied by TKI agent, dose and disease status (stable versus localised progressive disease). Rates of disease progression, surgical morbidity, mortality and adverse drug reactions were extracted from the existing literature. Deterministic sensitivity analyses were performed to examine changes in cost due to variations in key variables. RESULTS: The least-costly scenario was to perform no surgery. The most costly scenario was to perform surgery on patients with localised progressive disease on IM 800 mg. The overall range of costs clustered within approximately $47,000 (USD). Variations in surgical cost, surgical mortality and cost of IM demonstrated thresholds for changing the least-costly scenario within plausible tested ranges. CONCLUSION: Costs of surgical intervention at different time-points within the treatment course of patients with advanced GIST fluctuate within a relatively narrow range, suggesting that costs arise primarily from the administration of TKI. The decision to pursue cytoreductive surgery should not be based on cost alone. Future studies should incorporate health-state utilities when available.

Efficacy and economic value of adjuvant imatinib for gastrointestinal stromal tumors.

OBJECTIVE: This article presents the clinical effectiveness and cost-effectiveness of the use of adjuvant imatinib mesylate for treating patients with localized primary gastrointestinal stromal tumors (GISTs) and discusses the impact of prolonged treatment with adjuvant imatinib on health care costs. METHODS: A systematic review of the medical literature was conducted to explore recently reported clinical trials demonstrating the clinical benefit of adjuvant imatinib in GISTs, along with analyses discussing the economic impact of adjuvant imatinib. RESULTS: Two phase III trials have demonstrated a significant clinical benefit of adjuvant imatinib treatment in GIST patients at risk of recurrence after tumor resection. Guidelines now suggest adjuvant treatment for at least 3 years in patients at high risk of recurrence. Despite this clinical effectiveness, prolonged use of adjuvant imatinib can lead to an increase in the risk for adverse events and to increased costs for both patients and health care systems. However, the increased cost is partially offset by cost reductions associated with delayed or avoided GIST recurrences. Three years of adjuvant treatment in high-risk patients was concluded to be cost-effective. Therefore, the careful selection of patients who are most likely to benefit from treatment can lead to improved clinical outcomes and significant cost savings. CONCLUSION: Although introducing adjuvant imatinib has an economic impact on health plans, this effect seems to be limited. Several analyses have demonstrated that adjuvant imatinib is more cost-effective for treating localized primary GISTs than surgery alone. In addition, 3 years of adjuvant imatinib is more cost-effective than 1 year of adjuvant therapy.

Clinical effectiveness and cost-effectiveness of imatinib dose escalation for the treatment of unresectable and/or metastatic gastrointestinal stromal tumours that have progressed on treatment at a dose of 400 mg/day: a systematic review and economic evaluation.

BACKGROUND: Imatinib dose escalation is advocated for gastrointestinal stromal tumour (GIST) treatment, but its effectiveness compared with sunitinib and best supportive care (BSC) after failure at the 400 mg/day dose is unknown. OBJECTIVES: To assess the effectiveness and cost-effectiveness of imatinib at escalated doses of 600 or 800 mg/day for patients with unresectable and/or metastatic GISTs whose disease had progressed on 400 mg/day. DATA SOURCES: Electronic databases, including MEDLlNE, MEDLINE In-Process, EMBASE, BIOSIS, Science Citation Index, Health Management Information Consortium and the Cochrane Controlled Trials Register, were searched until September 2009. REVIEW METHODS: A systematic review of the literature was carried out according to standard methods. An economic model was constructed to assess the cost-effectiveness of seven alternative pathways for treating patients with unresectable and/or metastatic GISTs. RESULTS: Five primary studies involving 669 people were included for clinical effectiveness; four reported imatinib and one reported sunitinib. The data were essentially observational as none of the studies was designed to specifically assess treatment of patients whose disease had progressed on 400 mg/day imatinib. For 600 mg/day imatinib, between 26% and 42% of patients showed either a partial response (PR) or stable disease (SD). Median time to progression was 1.7 months (range 0.7-24.9 months). For 800 mg/day imatinib, between 29% and 33% of patients showed either a PR or SD. Median overall survival (OS) was 19 months [95% confidence interval (CI) 13 to 23 months]. Progression-free survival ranged from 81 days to 5 months (95% CI 2 to 10 months). Median duration of response was 153 days (range 37-574 days). Treatment progression led to 88% discontinuations but between 16% and 31% of patients required a dose reduction, and 23% required a dose delay. There was a statistically significant increase in the severity of fatigue (p < 0.001) and anaemia (p = 0.015) following dose escalation. For sunitinib, median OS was 90 weeks (95% CI 73 to 106 weeks). For the cost-effectiveness review, only one full-text study and one abstract were identified, comparing imatinib at an escalated dose, sunitinib and BSC, although neither was based on a UK context. The definition of BSC was not consistent across the studies, and the pattern of resources (including drugs for treatment) and measures of effectiveness also varied. Within the model, BSC (assumed to include continuing medication to prevent tumour flare) was the least costly and least effective. It would be the care pathway most likely to be cost-effective when the cost per quality-adjusted life-year threshold was < £25,000. Imatinib at 600 mg/day was most likely to be cost-effective at a threshold between £25,000 and £45,000. Imatinib at 600 mg/day followed by further escalation followed by sunitinib was most likely to be cost-effective at a threshold > £45,000. LIMITATIONS: The evidence base was sparse, data were non-randomised and potentially biased. The economic model results are surrounded by a considerable degree of uncertainty and open to biases of unknown magnitude and direction. CONCLUSIONS: Around one-third of patients with unresectable and/or metastatic GIST, who fail on 400 mg/day of imatinib, may show response or SD with escalated doses. Between a threshold of £25,000 and £45,000, provision of an escalated dose of imatinib would be most likely to be cost-effective. However, these results should be interpreted with caution owing to the limited evidence available on outcomes following imatinib dose escalation or sunitinib for this group of patients. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Imatinib as adjuvant treatment following resection of KIT-positive gastrointestinal stromal tumours.

This is a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of adjuvant imatinib post resection of KIT-positive gastrointestinal stromal tumours (GISTs) compared with resection only in patients at significant risk of relapse. The ERG report is based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The bulk of the clinical evidence submitted was in the form of one randomised controlled trial (RCT), the Z9001 trial, funded by the manufacturer, which compared resection + adjuvant imatinib for 1 year to resection only. Results were immature, with median recurrence-free survival (RFS) not yet having been reached at the time of analysis. The trial did provide evidence of a delay in disease recurrence [1-year RFS rate of 98% in the imatinib arm vs 83% in the placebo arm [hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.22 to 0.53, p < 0.0001)] but no evidence of an overall survival benefit. There was no long-term evidence around the rate of imatinib resistance over time with different treatment strategies (± adjuvant treatment). The relevant patient group for this appraisal is those at significant risk of relapse. These form a subgroup of the Z9001 trial, and all information regarding this group was designated 'Commercial-in-Confidence' (CIC). Median observation time for RFS was also CIC. The manufacturer constructed a Markov model comprising 10 health states designed to estimate costs and effects of treatment over a lifetime time horizon. The manufacturer's estimate of the base-case incremental cost-effectiveness ratio (ICER) was 22,937 pounds/quality-adjusted life-year (subsequently amended by the manufacturer to 23,601 pounds). While the structure of the model reasonably reflected the natural history of the disease, the ERG had numerous concerns regarding the selection of, and assumptions around, input parameters (utilities, monthly probabilities of recurrence and death). Furthermore, the model was set up in such a way that any delay in recurrence translated directly into a survival benefit, an assumption that has no evidence base. A further assumption not supported by evidence was that any treatment benefit gained in the first year is carried on for a further 2 years at the same rate. Appropriate probabilistic sensitivity analysis was undertaken on the base case only, but not on scenario analyses, or choice of model used to estimate long-term survival data. The model was not amenable to changes in input values, thus limiting any additional analyses by the ERG to test assumptions. Due to the large number of uncertainties and assumptions, the estimated ICERs should be regarded as highly uncertain. The guidance issued by NICE in June 2010 as a result of the STA does not recommend imatinib as adjuvant treatment after resection of gastrointestinal stromal tumours, although individuals currently receiving adjuvant imatinib should have the option to continue treatment until they and their clinician consider it appropriate to stop.

Budgetary impact of treatment with adjuvant imatinib for 1 year following surgical resection of Kit-positive localized gastrointestinal stromal tumors.

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.

Cost-effectiveness analysis of sunitinib in patients with metastatic and/or unresectable gastrointestinal stroma tumours (GIST) after progression or intolerance with imatinib.

INTRODUCTION: Sunitinib is a multiselective oral inhibitor of several tyrosine-kinase receptors that has demonstrated its efficacy in patients with metastatic and/or unresectable gastrointestinal stroma tumours (GIST) who were resistant to or intolerant to previous treatment with imatinib. The purpose of this study is to assess the cost-effectiveness of sunitinib vs. best supportive care (BSC) in GIST as a second- line treatment, from the perspective of the Spanish National Health System. MATERIALS AND METHODS: A Markov model was used to assess the cost effectiveness of sunitinib (50 mg/day, 4 weeks "on" and 2 weeks "off") vs. BSC in GIST as a second-line treatment. Transition probabilities between the three health states considered in the model (progression-free survival (PFS), progression and death) were obtained from a clinical trial [Demetri et al. (2006) Lancet 368:1329-1338]. Health resource data (drugs, medical visits, laboratory and radiology tests, palliative care and adverse events) were obtained from an expert panel. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Projected PFS years, life years (LY) and quality of life adjusted years (QALYs) were higher for sunitinib compared with BSC: 0.50 vs. 0.24, 1.59 vs. 0.88 and 1.00 vs. 0.55. Mean costs per patient were 23,259 euros with sunitinib and 1,622 euros with BSC. The incremental cost-effectiveness ratios (ICERs) obtained were: 4,090 euros/month PFS, 30,242 euros/LY and 49,090 euros/QALY gained. The most influential variables for the results were the efficacy and unit cost of sunitinib. CONCLUSIONS: According to the efficiency thresholds for oncology patients in developed countries, sunitinib is considered cost-effective vs. BSC with acceptable costs per LY and QALY gained.

Cost-effectiveness analysis of sunitinib in patients with metastatic and/or unresectable gastrointestinal stroma tumours (GIST) after progression or intolerance with imatinib

INTRODUCTION: Sunitinib is a multiselective oral inhibitor of several tyrosine-kinase receptors that has demonstrated its efficacy in patients with metastatic and/or unresectable gastrointestinal stroma tumours (GIST) who were resistant to or intolerant to previous treatment with imatinib. The purpose of this study is to assess the cost-effectiveness of sunitinib vs. best supportive care (BSC) in GIST as a second- line treatment, from the perspective of the Spanish National Health System. MATERIALS AND METHODS: A Markov model was used to assess the cost effectiveness of sunitinib (50 mg/day, 4 weeks "on" and 2 weeks "off") vs. BSC in GIST as a second-line treatment. Transition probabilities between the three health states considered in the model (progression-free survival (PFS), progression and death) were obtained from a clinical trial [Demetri et al. (2006) Lancet 368:1329-1338]. Health resource data (drugs, medical visits, laboratory and radiology tests, palliative care and adverse events) were obtained from an expert panel. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Projected PFS years, life years (LY) and quality of life adjusted years (QALYs) were higher for sunitinib compared with BSC: 0.50 vs. 0.24, 1.59 vs. 0.88 and 1.00 vs. 0.55. Mean costs per patient were 23,259 euros with sunitinib and 1,622 euros with BSC. The incremental cost-effectiveness ratios (ICERs) obtained were: 4,090 euros/month PFS, 30,242 euros/LY and 49,090 euros/QALY gained. The most influential variables for the results were the efficacy and unit cost of sunitinib. CONCLUSIONS: According to the efficiency thresholds for oncology patients in developed countries, sunitinib is considered cost-effective vs. BSC with acceptable costs per LY and QALY gained (AU)

No disponible

Verification of imatinib cost-effectiveness in advanced gastrointestinal stromal tumor in British Columbia (VINCE-BC study).

BACKGROUND: This cost-effectiveness analysis of imatinib in British Columbia Cancer Agency (BCCA) patients with advanced gastrointestinal stromal tumors (GIST) was performed to justify funding. PATIENTS AND METHODS: A pragmatic, retrospective review identified BCCA patients with advanced GIST who received imatinib or historical treatment during successive, pre-specified time periods. Primary outcome was the cost-effectiveness (CE) of imatinib based on median overall survival (MOS). Secondary outcomes were cost-effectiveness based on median progression-free survival (PFS) and comparison to literature efficacy. This study took the BCCA perspective. Sensitivity analyses varying effectiveness over the 95% confidence interval (CI), cost to its extremes, discounting level at 0, 3, and 5%, and substituting life expectancy for MOS were performed. RESULTS: Forty-six and 47 patients in the imatinib and historical groups respectively showed MOS with imatinib to be 66.7 months (95%CI 61.7- infinity) compared to 7.7 (95%CI 6.0-12.6) in the historical group. Median-PFS were 45.3 months (95%CI 24.4-infinity) and 5.6 (95%CI 3.5-8.5) respectively. Imatinib effectiveness was similar to literature reports. The annual incremental CE ratio for imatinib was $15,882 CDN per median life year gained and $23,603 CDN per median year of PFS. CONCLUSIONS: Imatinib for advanced GIST seems cost-effective in BC. RESULT: were robust across a range of sensitivity analyses.

The challenge of conducting pharmacoeconomic evaluations in oncology using crossover trials: the example of sunitinib for gastrointestinal stromal tumour.

This paper examines the challenge of conducting economic evaluations to support patient access to cancer therapies when the cost-effectiveness estimation is hampered by crossover trial design. To demonstrate these limitations, we present the submission to the Canadian Drug Review (CDR) of a cost-effectiveness evaluation of sunitinib versus best supportive care (BSC) for the treatment of gastrointestinal stromal tumour in patients intolerant or resistant to imatinib. The economic model generated an incremental cost-effectiveness ratio for sunitinib versus BSC of dollars 79,884/quality-adjusted life-year gained. Eight months after initial submission, CDR granted a final recommendation to fund sunitinib following the manufacturer's appeal against their first recommendation. Although cost-effectiveness is an important consideration in reimbursement decisions, there is a need for improved decision-making processes for cancer drugs, as well as a better understanding of the limitations of clinical trial design.

The epidemiologic, health-related quality of life, and economic burden of gastrointestinal stromal tumours.

BACKGROUND AND OBJECTIVES: Gastrointestinal stromal tumours (GIST) are uncommon tumours believed to arise from interstitial cells of Cajal or their precursors in the gastrointestinal (GI) tract, accounting for a small percentage of GI neoplasms and sarcomas. Given the recent recognition of GIST as a distinct cancer, as well as new treatment options available today, a review of the epidemiologic, health-related quality of life (HRQL), and economic burden of GIST is timely from a payer, provider and patient perspective and may provide guidance for treatment decision making and reimbursement. METHODS: A systematic literature review of PubMed and five scientific meeting databases, was conducted to identify published studies and abstracts describing the epidemiologic, HRQL and economic impact of GIST. Publications deemed worthy of further review, based on the information available in the abstract, were retrieved in full text. RESULTS AND DISCUSSION: Thirty-four publications met the review criteria: 29 provided data on GIST epidemiology, one provided cost data, three reported HRQL outcomes, and one reported cost and HRQL outcomes. The annual incidence of GIST (cases per million) ranged from 6.8 in the USA to 14.5 in Sweden, with an estimated 5-year survival rate of 45-64%. On the Functional Illness of Chronic Therapy-fatigue instrument, GIST patients scored 40.0 compared with 37.6 in anaemic cancer patients (0 = worst; 52 = least fatigue). Total costs over 10 years for managing GIST patients with molecularly targeted treatment was estimated at pounds 47 521- pounds 56 146 per patient compared with pounds 4047- pounds 4230 per patient with best supportive care. CONCLUSIONS: The incidence of GIST appears to be similar by country; the lower estimate in one country could be explained by differences in method of case ascertainment. Data suggest that the HRQL burden of GIST is similar to that with other cancers although this requires further exploration. The value of new therapies in GIST needs to consider not only cost but also anticipated benefits and the unmet medical need in this condition.