Cost effectiveness of imatinib mesylate in the treatment of advanced gastrointestinal stromal tumours.
ABSTRACT Imatinib mesylate is the first effective therapy for advanced unresectable gastrointestinal stromal tumours (GIST). Adoption of this therapy in clinical practice is partly dependent on reimbursement by third-party payers in many countries. The objective of this study was to estimate the cost effectiveness of imatinib mesylate in the treatment of GIST.
A cost-effectiveness model of GIST treatment was developed. Long- term survival and duration of imatinib mesylate benefit were projected by fitting curves to 52-month follow-up data from a phase II clinical trial of imatinib and projecting weekly probabilities of survival and continued treatment over 10 years. Weekly cost estimates in 2005 US dollars included cost of imatinib mesylate 400 mg/day ($US685), other medical services for imatinib mesylate-treated patients ($US359) and palliative care for patients in the end stage of GIST ($US2575). Utility associated with successful treatment was estimated at 0.935 and that of treatment failure and progressive disease at 0.875. Costs, life-years and quality- adjusted life-years (QALYs) were calculated over the 10-year time horizon and discounted to treatment initiation at an annual rate of 3%.
Imatinib mesylate therapy for unresectable GIST was projected to increase life expectancy to 5.8 years, an increase of 2.7 years over the control group. This translated into an increase of 1.9 QALYs at a marginal cost of $US74 369, yielding a cost-effectiveness ratio of $US38 723 per QALY. Cost effectiveness was not very sensitive to model parameters other than the cost of imatinib mesylate itself.
The cost effectiveness of imatinib mesylate in the treatment of GIST is within the commonly accepted range for life-saving interventions, based on US data.
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ABSTRACT: The interpretation of time trends and geographical differences of population-based survival rates is generally not easy, due to the difficulty in disentangling the effects of observational biases, diagnostic and therapeutic procedures and their interactions. Whereas descriptive analysis of relative survival is generally based on survival levels estimated at fixed time since diagnosis, interpretation issues can take advantage from the analysis of the shape of the considered relative survival. Parametric survival models allowing the estimation of the fraction of cured patients are applied here to analyze and discuss the differences in colon cancer relative survival between European countries, according to age and period of diagnosis. The survival curves of colon cancer patients are described according to 2 parameters: the proportion of cured patients and the mean survival time of fatal cases. These parameters are estimated by least square nonlinear regression of relative survival values derived from the EUROCARE Project publication. Exponential and Weibull survival functions are used to model the relative survival curve for the fraction of fatal cases. The Weibull model gives generally a better fit with respect to the exponential model, thus indicating that the mortality rate for fatal cases is decreasing with time since diagnosis. For the youngest patients, however, the 2 survival functions give practically overlapping estimates. The overall proportion of colon cancer patients in Europe that are estimated to be cured was 38.6%. This proportion increased from 36% to 40% for patients diagnosed in 1978-1980 and in 1983-1985, respectively. Accordingly, mean survival time of fatal cases increased from 1.18 to 1.52 years. According to age, the proportion of cured patients present a marked decrease from young (48.4% at age 15-44 years) to middle-aged patients (38.6% at age 5564 years) and only a mild decrease from these to the oldest patients (34.4% at age 75 or more). The opposite effect was shown by survival time of fatal cases, i.e., 1.71, 1.75 and 0.77 years for the same age classes, respectively. Proportion of cured cases and mean survival time of fatal cases tended to be positively correlated with each other across countries. Our results are consistent with the hypothesis that a real improvement in colon cancer survival took place in Europe during the years 1978-1985 and also suggest that the well-known decrease of relative survival with age at diagnosis could be mostly due to a decreasing efficacy of early diagnosis for patients under 60 years old and to less effective therapies for older patients.International Journal of Cancer 08/1998; 77(3):322-9. · 6.20 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumors (GIST) are rare tumors of the gastrointestinal (GI) tract that arise from primitive mesenchymal cells. GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. The majority of GISTs are immunohistochemically positive for c-kit protein (CD 117) and CD34. GISTs express a heterogeneous clinical course not easily predicted by standard pathological means. The most important prognostic factors are size > 5 cm, tumor necrosis, infiltration and metastasis to other sites, mitotic count > 1-5 per 10 high-powered fields, and most recently, mutation in the c-kit gene. Surgical resection remains the mainstay of treatment, as chemotherapy and radiation are ineffective. Long-term follow-up is imperative, as recurrence rates are high.Annals of Surgical Oncology 10/2000; 7(9):705-12. · 4.12 Impact Factor
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ABSTRACT: Background: Primary gastrointestinal sarcomas are uncommon, and the clinicopathological determinants of survival remain unclear. In order to correlate clinical presentation, pathological assessment, and treatment with outcome, we have analyzed our institution's recent experience with these tumors. Methods: Records of adult patients admitted to our institution between July 1982 and December 1991 were reviewed. Results: During this period, 38 adult patients (>16 years of age) were admitted to our institution with a primary gastrointestinal sarcoma. They accounted for 2% of all adult sarcoma admissions during that period. The study population was composed of 26 men and 12 women. Ages ranged from 29 to 82 years (mean 59). Disease was localized to the primary site in 30 patients (81%). The stomach was the most frequent site of disease (20 cases). The small bowel was affected in nine cases (five duodenum, four jejunum) and the large bowel in nine cases (two colon, seven rectum). Ninety-two percent of patients were symptomatic at presentation. A complete resection was performed in 27 cases, incomplete resection in seven cases, and biopsy only in the remaining three patients. Nine patients received doxorubicin-based chemotherapy. Leiomyosarcoma (n=35) was the predominant histological diagnosis. Twenty-six tumors were classified as high grade (68%) and 12 as low grade (32%). Overall actuarial 5-year survival was 28% (median follow-up 26 months). Weight loss (p=0.02) and pain at presentation (p=0.05) were adverse prognostic factors. Histological grade (p=0.0002), completeness/extent of surgical resection (p=0.005), or a small bowel primary site were significant determinants of overall survival. The resection of contiguous organs did not affect survival if the primary tumor was completely excised (p=0.422). Age, race, sex, presentation (prior surgery), tumor size, or adjuvant therapy were not significant prognostic factors. Recurrence was noted in 44% after complete resection, and mean time to recurrence was 9 months (median 7, range <1–37). Hepatic metastases (42%) and local recurrence (42%) were the predominant sites of initial failure. For patients with a complete resection, grade was the major prognostic determinant (5-year survival: high grade/complete resection 18% vs. low grade/complete resection 72%, p=0.002). Conclusion: The prognosis of gastrointestinal sarcomas is poor. Complete surgical excision is the optimal therapy. However, our results suggest that surgery alone is inadequate for high-grade tumors. We believe that these patients should be considered candidates for investigational adjuvant therapies.Annals of Surgical Oncology 12/1994; 2(1):26-31. · 4.12 Impact Factor