Evidence map›Paper›PMID 25378911›Full record

SynthesisDrug design, development and therapy2014

Clinical efficacy of second-generation tyrosine kinase inhibitors in imatinib-resistant gastrointestinal stromal tumors: a meta-analysis of recent clinical trials.

Lile Wu, Zhongqiang Zhang, Hongliang Yao, Kuijie Liu, Yu Wen, Li Xiong

Abstract readMeta-Analysis
In one paragraph

Synthesis in Drug design, development and therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
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  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Lile WuDepartment of General Surgery, Second Xiangya Hospital of Central South University, Changsha, People's Republic of China.
Zhongqiang ZhangDepartment of General Surgery, Second Xiangya Hospital of Central South University, Changsha, People's Republic of China.
Hongliang YaoDepartment of General Surgery, Second Xiangya Hospital of Central South University, Changsha, People's Republic of China.
Kuijie LiuDepartment of General Surgery, Second Xiangya Hospital of Central South University, Changsha, People's Republic of China.
Yu WenDepartment of General Surgery, Second Xiangya Hospital of Central South University, Changsha, People's Republic of China.
Li XiongDepartment of General Surgery, Second Xiangya Hospital of Central South University, Changsha, People's Republic of China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPrimary and secondary resistance to imatinib, a selective receptor tyrosine kinase inhibitor (TKI), is a serious clinical problem in the control of advanced gastrointestinal stromal tumors (GIST). Here we report on a meta-analysis we performed to evaluate the efficacy of second-generation TKIs in the treatment of patients with imatinib-resistant GIST.

methodsRandomized controlled trials evaluating the clinical efficacy of second-generation TKIs were identified by searching PubMed and EMBASE from 2000 to February 2014. Outcomes subjected to analysis were progression-free survival and overall survival. Statistical analyses were performed using Review Manager version 5.1.0 (Cochrane Collaboration, Oxford, UK). Weighted hazard ratios (HR) with 95% confidence intervals (CIs) were calculated for the outcomes. Fixed-effects or random-effects models were used, depending on the degree of heterogeneity across the selected studies.

resultsThree randomized controlled trials were selected for meta-analysis. Among imatinib-resistant or imatinib-intolerant patients, 541 received second-generation TKIs (sunitinib, nilotinib, or regorafenib) and 267 controls received placebo or best supportive care. Progression-free survival was significantly improved in the TKI-treated group (HR 0.38; 95% CI 0.24-0.59; P<0.0001). No statistically significant difference was detected in overall survival between the treatment group and the control group (HR 0.85; 95% CI 0.71-1.03; P=0.09). In the subgroup of patients who were resistant or intolerant to both imatinib and sunitinib, TKI therapy (nilotinib or regorafenib) improved progression-free survival (HR 0.40; 95% CI 0.19-0.84; P=0.02) but not overall survival (HR 0.83; 95% CI 0.63-1.08; P=0.17). Regorafenib was shown to be effective in terms of progression-free survival across different subpopulations of patients who were resistant to both imatinib and sunitinib.

conclusionSecond-generation TKIs (sunitinib, nilotinib, and regorafenib) are effective in improving progression-free survival but not overall survival in patients with GIST who are resistant or intolerant to imatinib or to imatinib and sunitinib. Regorafenib is promising as a third-line treatment option for patients with advanced GIST.

Indexed as

Drug Resistance, NeoplasmAntineoplastic AgentsBenzamidesGastrointestinal NeoplasmsGastrointestinal Stromal TumorsHumansImatinib MesylateIndolesPhenylurea CompoundsPiperazinesProtein Kinase InhibitorsProtein-Tyrosine KinasesPyridinesPyrimidinesPyrrolesRandomized Controlled Trials as TopicAntineoplastic AgentsBenzamidesImatinib MesylateIndolesnilotinibPhenylurea CompoundsPiperazinesProtein Kinase InhibitorsProtein-Tyrosine KinasesPyridinesPyrimidinesPyrrolesregorafenibSunitinibgastrointestinal stromal tumorimatinibnilotinibregorafenibtyrosine kinase inhibitor

Identifiers

PMID25378911
PMCPMC4219427

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.