Tyrosine kinase inhibitor combination therapy in first-line treatment of non-small-cell lung cancer: systematic review and network meta-analysis.
Tyrosine kinase inhibitor combination therapy in first-line treatment of non-small-cell lung cancer: systematic review and network meta-analysis.
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DOI：
10.2147/ott.s134382
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发表时间：
2017
影响因子：
4
通讯作者：
Reguart N
中科院分区：
文献类型：
--
作者：
Batson S;Mitchell SA;Windisch R;Damonte E;Munk VC;Reguart N
表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)的引入改善了EGFR+突变的晚期非小细胞肺癌(NSCLC)患者的前景。然而，大多数患者出现了耐药性，结果是中位无进展生存期(PFS)为12个月ŝ。联合使用EGFR-TKI和其他药物，如贝伐单抗，是一种有希望的延长缓解的方法。这项系统回顾和网络荟萃分析(NMA)被用来评估关于晚期NSCLC患者使用EGFR-TKI一线联合治疗的益处的现有证据。使用相关检索词进行文献检索。使用已发表的算法，从数字化的Kaplan-Meier曲线数据重建研究水平的伪个体患者水平数据(IPD)。应用比例风险模型和加速失效时间(AFT)生存模型对研究对象的IPD进行分析，得出加速失效时间(AFT)模型是最合适的模型。使用贝叶斯框架，基于加速因子(AFS)进行NMA，以比较EGFR-TKI和化疗。确定了9项随机对照试验，为EGFR+肿瘤患者的EGFR-TKI治疗提供了数据。这些研究包括阿法替尼(n=3)、厄洛替尼(n=3)、厄洛替尼加贝伐单抗(n=1)和吉非替尼(n=2)。与化疗相比，厄洛替尼+贝伐单抗的PFS增加最大，1/AF为0.24(95%可信区间[CRI]0.17，0.34)。与EGFR-TKI单药治疗相比，这种联合治疗也产生了更大的PFS增加：1/AF与afatinib相比，0.51(95%CRI 0.35，0.73)；与erlotinib，0.53(95%CRI 0.39，0.72)；与Gefitinib，0.46(95%CRI 0.32，0.66)。与化疗相比，三种EGFR-TKI单一疗法均延长了PFS；吉非替尼的疗效估计为1/AF 0.53(95%CRI 0.48，0.60)，厄洛替尼的疗效估计为1/AF 0.46(95%CRI 0.40，0.53)。没有证据表明EGFR-TKI单一疗法之间的差异，因为所有95%的CRI都包括零值。尽管erlotinib加贝伐单抗的数据来自单一的2期研究，但NMA的结果表明，在erlotinib的基础上加用贝伐单抗可能是改善EGFR-TKI单一疗法在晚期EGFR+非小细胞肺癌患者中取得的结果的一种有前景的方法。
The introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced non-small-cell lung cancer (NSCLC) with EGFR+ mutations. However, most patients develop resistance, with the result that median progression-free survival (PFS) iŝ12 months. Combining EGFR-TKIs with other agents, such as bevacizumab, is a promising approach to prolonging remission. This systematic review and network meta-analysis (NMA) were undertaken to assess available evidence regarding the benefits of first-line combination therapy involving EGFR-TKIs in patients with advanced NSCLC. Literature searches were performed using relevant search terms. Study-level pseudo-individual patient-level data (IPD) were recreated from digitized Kaplan–Meier curve data, using a published algorithm. Study IPD were analyzed using both the proportional hazards and the acceleration failure time (AFT) survival models, and it was concluded that the AFT model was most appropriate. An NMA was performed based on acceleration factors (AFs) using a Bayesian framework to compare EGFR-TKIs and chemotherapy. Nine randomized controlled trials were identified that provided data for EGFR-TKI therapy in patients with EGFR+ tumors. These included studies of afatinib (n=3), erlotinib (n=3), erlotinib plus bevacizumab (n=1) and gefitinib (n=2). Erlotinib plus bevacizumab produced the greatest increase in PFS compared with chemotherapy, with 1/AF being 0.24 (95% credible interval [CrI] 0.17, 0.34). This combination also produced greater increases in PFS compared with EGFR-TKI monotherapy: 1/AF versus afatinib, 0.51 (95% CrI 0.35, 0.73); versus erlotinib, 0.53 (95% CrI 0.39, 0.72) and versus gefitinib, 0.46 (95% CrI 0.32, 0.66). All three EGFR-TKI monotherapies prolonged PFS compared with chemotherapy; estimates of treatment effect ranged from 1/AF 0.53 (95% CrI 0.48, 0.60) for gefitinib to 1/AF 0.46 (95% CrI 0.40, 0.53) for erlotinib. There was no evidence for differences between EGFR-TKI monotherapies, as all 95% CrIs included the null value. Although data for erlotinib plus bevacizumab came from a single Phase 2 study, the results of the NMA suggest that adding bevacizumab to erlotinib may be a promising approach to improving the outcomes achieved with EGFR-TKI monotherapy in patients with advanced EGFR+ NSCLC.