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

• Published in: Drug design, development and therapy development and therapy, 2014-01, Vol.8 (default), p.2061-2067
• Main Authors: Wu, Lile, Zhang, Zhongqiang, Yao, Hongliang, Liu, Kuijie, Wen, Yu, Xiong, Li
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Benzamides - chemistry; Benzamides - pharmacology; Benzamides - therapeutic use; Clinical trials; Confidence intervals; Control methods; Drug Resistance, Neoplasm - drug effects; Drug therapy; Effectiveness; Enzyme inhibitors; Gastrointestinal cancer; Gastrointestinal Neoplasms - drug therapy; Gastrointestinal Neoplasms - pathology; gastrointestinal stromal tumor; Gastrointestinal Stromal Tumors - drug therapy; Gastrointestinal Stromal Tumors - pathology; Gastrointestinal tumors; Health aspects; Heterogeneity; Humans; Imatinib; Imatinib Mesylate; Indoles - chemistry; Indoles - pharmacology; Indoles - therapeutic use; Inhibitor drugs; Kinases; Medical research; Meta-analysis; Mutation; nilotinib; Original Research; Patients; Phenylurea Compounds - chemistry; Phenylurea Compounds - pharmacology; Phenylurea Compounds - therapeutic use; Physiological aspects; Piperazines - chemistry; Piperazines - pharmacology; Piperazines - therapeutic use; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein kinases; Protein-tyrosine kinase receptors; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyridines - chemistry; Pyridines - pharmacology; Pyridines - therapeutic use; Pyrimidines - chemistry; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Pyrroles - chemistry; Pyrroles - pharmacology; Pyrroles - therapeutic use; Randomization; Randomized Controlled Trials as Topic; regorafenib; Statistical analysis; Subgroups; Subpopulations; Sunitinib; Survival; Targeted cancer therapy; Treatment Outcome; Tumors; Tyrosine; tyrosine kinase inhibitor; Vascular endothelial growth factor
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S63840

Primary 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. Randomized 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. Three 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