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| Ref Type | Journal Article | ||||||||||||
| PMID | (20124181) | ||||||||||||
| Authors | Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST) | ||||||||||||
| Title | Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. | ||||||||||||
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| Abstract Text | The Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST) project aims to additionally explore the data of the two large, randomized, cooperative-group studies comparing two doses of imatinib (400 mg daily v twice daily) in 1,640 patients with advanced GIST.End points were progression-free survival (PFS) and overall survival (OS). Investigated cofactors included age, sex, performance status (PS), primary tumor site, time from diagnosis, prior therapies, baseline biology, and KIT/PDGFRalpha mutations for a subset of 772 patients. Univariate and multivariate models were used for the analysis.At a median follow-up of 45 months, a small but significant PFS advantage was documented for the high-dose arm. OS was identical in the two arms. The multivariate prognostic models included the following adverse factors: male sex, poor PS, and high baseline neutrophils counts (PFS and OS); low hemoglobin and GIST from small bowel origin (PFS); and advanced age, large tumor size, low albumin level, and prior chemotherapy (OS). In patients analyzed for mutations, patients with wild type, patients with KIT exon 9 mutations, and patients with other mutations had worse prognoses than patients with KIT exon 11 mutations for both end points. The mutation status was the only predictive factor for the PFS benefit attributed to high-dose treatment that resulted in significantly longer PFS (and higher objective response rate) for patients with KIT exon 9 mutations.This analysis confirms a small PFS advantage of high-dose imatinib, essentially among patients with KIT exon 9 mutations, but no OS advantage. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| KIT exon9 | gastrointestinal stromal tumor | sensitive | Imatinib | Clinical Study - Meta-analysis | Actionable | In a meta-analysis of two phase III trials (MetaGIST), high-dose Gleevec (imatinib) treatment in patients with gastrointestinal stromal tumors harboring KIT exon 9 mutations resulted in a similar overall survival (p=0.15) but an increased progression-free survival (HR=0.58, p=0.017) and increased best overall response rate (47% vs 21%, p=0.0037) compared to low-dose Gleevec (imatinib) treatment (PMID: 20124181; NCT00685828, NCT00009906). | 20124181 |