Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs)

Rutkowski, Piotr; Nowecki, Zbigniew; Dębiec‐Rychter, Maria; Grzesiakowska, Urszula; Michej, Wanda; Woźniak, Agnieszka; Siedlecki, Janusz A.; Limon, Janusz; Dobosz, Anna Jerzak vel; Kąkol, Michał; Osuch, Czesław; Ruka, W.

doi:10.1007/s00432-007-0202-4

Cited by 32 publications

(23 citation statements)

References 29 publications

(31 reference statements)

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“…We have previously identified some predictive factors for the benefit of imatinib therapy in terms of inhibition of disease progression in advanced GIST [26]. Also, van Glabbeke and co-authors [27] had reported data on distinctive predictive clinicopathological factors for initial and late resistance to imatinib in advanced GISTs, but this analysis did not include the genotyping of the tumor as well as the strategy of removal of residual disease during therapy with tyrosine kinase inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…These factors may account for the basis for development of the nomogram for PFS and OS [28]. Laboratory factors as high granulocyte count, low hemoglobin level, or low albumin level together with poor general performance status were previously implied as predictive factors for resistance to imatinib therapy [12, 13, 17, 18, 23, 26, 27]. Consistently with the results of present series, these factors can be related to generally more advanced and aggressive tumors, with higher inflammatory component influencing pharmacokinetics of the drug [13, 17, 27, 29, 30].…”

Section: Discussionmentioning

confidence: 99%

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What are the current outcomes of advanced gastrointestinal stromal tumors: who are the long-term survivors treated initially with imatinib?

et al. 2013

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The introduction of imatinib to clinical practice revolutionized therapy of advanced gastrointestinal stromal tumors (GIST), but its long-term results have been only just collected. We have attempted to identify factors related to the long-term survival. We have analyzed the data of 430 inoperable/metastatic/recurrent GIST patients treated with imatinib in reference centers, assessed the factors influencing the long-term overall survival (OS), and compared the outcomes in three periods of initiation of imatinib therapy during one decade (2001–2003, 2004–2006, 2007–2010). During analyzed time periods, we have found decrease in median largest tumor size at the start of imatinib therapy: 90.5 mm (2001–2003) versus 74 mm (2004–2006) versus 58 mm (2007–2010) (p = 0.002). Median progression-free survival (PFS) on 1st line imatinib was 37.5 months, without differences in PFS between three groups. Median OS was 5.8 years, 8-year OS rate was 43 %, and no difference in OS was demonstrated for patients treated in analyzed time periods. Independent good prognostic factors for longer OS were as follows: surgery of residual disease, initial WHO performance status 0/1, normal baseline albumin level, and the presence of exon 11 KIT mutations. Current median OS in advanced GIST reaches 6 years. The long-term survivors were characterized by smaller maximal tumors at imatinib start, better blood tests results, better performance status, and the surgical removal of residual disease. The latter might reduce the impact of tumor size and equalize the long-term results of therapy during last decade from introduction of imatinib. After introduction of subsequent lines of therapy (as sunitinib), the effect of primary mutational status on the long-term OS is also less visible.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

What are the current outcomes of advanced gastrointestinal stromal tumors: who are the long-term survivors treated initially with imatinib?

et al. 2013

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“…Despite these excellent results complete responses are rare (less than 10%), and most patients who initially respond ultimately acquire resistance via additional mutations in KIT. The median time to progression is roughly two to three years [68,70-72], although it is longer in other series [73]. …”

Section: Introductionmentioning

confidence: 99%

Current management and prognostic features for gastrointestinal stromal tumor (GIST)

et al. 2012

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Stromal or mesenchymal neoplasms affecting the gastrointestinal (GI) tract have undergone a remarkable evolution in how they are perceived, classified, approached, diagnosed and managed over the last 30 years. Gastrointestinal stromal tumors (GIST) account for approximately 1% to 3% of all malignant GI tumors. The clinical features can vary depending on the anatomic location, size and aggressiveness of the tumor. Metastatic GIST represents a successful example of molecular targeted therapy. In this comprehensive review, we discuss the epidemiology, clinical features and diagnostic modalities for GIST. We also describe treatment options for early stage, locally advanced and metastatic GIST. Indications for neoadjuvant and adjuvant therapy along with duration of therapy are also explained. A brief discussion of latest biomarkers and updates from recent meetings is also provided.

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“…Upon further review, 21 articles were eliminated due to inadequate data for meta-analysis or duplicate patient population. Finally, 15 studies published between 2001 and 2012 met the inclusion criteria [10-12,14-25]. Quality assessment was performed on 12 cohort studies using Newcastle–Ottawa Scale (mean score 6.75 ± 0.45) and 3 RCT studies using Jadad Scale (mean score 4.67 ± 0.58) (Table S2, Table S3).…”

Section: Resultsmentioning

confidence: 99%

“…The response rates (CR+PR) of different genotypes to Imatinib were tested in 9 reliable studies (group 1 [10,12,14,16,19,22–25]:). Overall meta-analysis showed that the pooled ORs of KIT exon 11-mutant group vs KIT exon 9-mutant group, KIT exon 11-mutant group vs wild type group and KIT exon 9-mutant group vs wild type group were 3.518 (95% CI: 2.556-4.843, p<0.001), 3.521 (95% CI: 1.731-7.165, p=0.001) and 0.981 (95% CI: 0.515-1.868, p=0.953), respectively (Table 2).…”

Section: Resultsmentioning

confidence: 99%

Practical Role of Mutation Analysis for Imatinib Treatment in Patients With Advanced Gastrointestinal Stromal Tumors: A Meta-Analysis

et al. 2013

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BackgroundImatinib has become the standard first line treatment of gastrointestinal stromal tumors (GIST) in the advanced phase and adjuvant setting. We carried out an up-to-date meta-analysis to determine the practical role of mutation analysis for imatinib treatment in patients with advanced GIST.MethodsEligible studies were limited to imatinib treatment for patients with advanced GIST and reported on mutation analysis. Statistical analyses were conducted to calculate the odds ratio (OR), hazard ratio (HR) and 95% confidence interval (CI) using fixed-effects and random-effects models.ResultsA total of 2834 patients from 3 randomized controlled trials and 12 cohort studies were included. The ORs of response rates in KIT exon 11-mutant GISTs were 3.504 (95% CI 2.549-4.816, p<0.001) and 3.521 (95% CI 1.731-7.165, p=0.001) compared with KIT exon 9-mutant and wild type GISTs, respectively. The HRs of progression-free survival in KIT exon 11-mutant GISTs were 0.365 (95% CI 0.301-0.444, p<0.001) and 0.375 (95% CI 0.270-0.519, p<0.001) compared with KIT exon 9-mutant and wild type GISTs. The HRs of overall survival in KIT exon 11-mutant GISTs were 0.388 (95% CI 0.293-0.515, p<0.001) and 0.400 (95% CI 0.297-0.538, p<0.001) compared with KIT exon 9-mutant and wild type GISTs. No statistical significant differences were found between KIT exon 9-mutant and wild type. The overall response rate in KIT-exon 11-mutant GISTs were 70.5% (65%-75.9%) compared with 57.1% (51%-63.2%) in KIT-positive GISTs. No evidence of publication bias was observed.ConclusionPatients with advanced GIST harboring a KIT exon 11 mutation have the best response rate and long-term survival with imatinib treatment. Mutation analysis would be more helpful than KIT expression analysis to decide appropriate therapy for a specific patient.

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Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs)

Abstract: We confirmed that many advanced GIST patients benefit from IM therapy for a prolonged time, although resistance to therapy is observed. We identified four independent biological factors influencing the PFS during long-term IM therapy.

Cited by 32 publications

References 29 publications

What are the current outcomes of advanced gastrointestinal stromal tumors: who are the long-term survivors treated initially with imatinib?

What are the current outcomes of advanced gastrointestinal stromal tumors: who are the long-term survivors treated initially with imatinib?

Current management and prognostic features for gastrointestinal stromal tumor (GIST)

Practical Role of Mutation Analysis for Imatinib Treatment in Patients With Advanced Gastrointestinal Stromal Tumors: A Meta-Analysis

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