Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.
Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.
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DOI：
10.1371/journal.pone.0085245
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Liang W;Wu X;Fang W;Zhao Y;Yang Y;Hu Z;Xue C;Zhang J;Zhang J;Ma Y;Zhou T;Yan Y;Hou X;Qin T;Dinglin X;Tian Y;Huang P;Huang Y;Zhao H;Zhang L
几种EGFR酪氨酸激酶抑制剂(EGFR-TKI)，包括erlotinib、gefitinib、afatinib和icotinib，目前可用于治疗携带EGFR突变的晚期非小细胞肺癌(NSCLC)患者。然而，这些TKI之间在突变人群中的正面试验还没有报道，这为间接和综合比较提供了空间。我们在电子数据库中搜索符合条件的文献。统计客观有效率(ORR)、无进展生存期(PFS)、总生存期(OS)。针对不同的结果建立了适当的网络，以纳入所有证据。基于贝叶斯网络的多治疗比较(MTCs)综合了所有纳入治疗的疗效和毒副作用。共纳入12项III期随机对照试验，研究对象为1821名有EGFR突变的参与者。直接Meta分析显示，对于突变患者，EGFR-TKIs的加权合并ORR值和1年PFS显著优于标准化疗组(ORR值：66.6%比30.9%，OR5.46，95%CI3.59比8.3，P<；0.00001；1年PFS：42.9%比9.7%，OR7.83，95%CI4.50比13.61；P<；0.00001)。在网络荟萃分析中，在所有结果指标上，这四种TKI之间的疗效没有统计学上的显著差异。秩概率趋势分析显示，最有效的累积治疗概率为(ORR、1年PFS、1年OS、2年OS)：厄洛替尼(51%，38%，14%，19%)，吉非替尼(1%，6%，5%，16%)，阿法替尼(29%，27%，30%，27%)和伊考替尼(19%，29%，NA，NA)。然而，与吉非替尼和伊考替尼相比，阿法替尼和埃洛替尼表现出更严重的皮疹和腹泻。目前的研究表明，对于EGFR突变的患者，厄洛替尼、吉非替尼、阿法替尼和伊考替尼的疗效相同，但呈现不同的疗效-毒性模式。与吉非替尼和伊考替尼相比，厄洛替尼和阿法替尼显示出潜在更好的疗效，但毒性显著更高。
Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including erlotinib, gefitinib, afatinib and icotinib are currently available as treatment for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, no head to head trials between these TKIs in mutated populations have been reported, which provides room for indirect and integrated comparisons. We searched electronic databases for eligible literatures. Pooled data on objective response rate (ORR), progression free survival (PFS), overall survival (OS) were calculated. Appropriate networks for different outcomes were established to incorporate all evidences. Multiple-treatments comparisons (MTCs) based on Bayesian network integrated the efficacy and specific toxicities of all included treatments. Twelve phase III RCTs that investigated EGFR-TKIs involving 1821 participants with EGFR mutation were included. For mutant patients, the weighted pooled ORR and 1-year PFS of EGFR-TKIs were significant superior to that of standard chemotherapy (ORR: 66.6% vs. 30.9%, OR 5.46, 95%CI 3.59 to 8.30, P<0.00001; 1-year PFS: 42.9% vs. 9.7%, OR 7.83, 95%CI 4.50 to 13.61; P<0.00001) through direct meta-analysis. In the network meta-analyses, no statistically significant differences in efficacy were found between these four TKIs with respect to all outcome measures. Trend analyses of rank probabilities revealed that the cumulative probabilities of being the most efficacious treatments were (ORR, 1-year PFS, 1-year OS, 2-year OS): erlotinib (51%, 38%, 14%, 19%), gefitinib (1%, 6%, 5%, 16%), afatinib (29%, 27%, 30%, 27%) and icotinib (19%, 29%, NA, NA), respectively. However, afatinib and erlotinib showed significant severer rash and diarrhea compared with gefitinib and icotinib. The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR-mutated patients. Erlotinib and afatinib revealed potentially better efficacy but significant higher toxicities compared with gefitinib and icotinib.
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影响因子：
51.1
作者：
Mitsudomi, Tetsuya;Morita, Satoshi;Fukuoka, Masahiro
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45.3
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