Lin Jia-Zhou, Ma Song-Kun, Wu Sheng-Xi, Yu Shu-Han, Li Xu-Yuan
Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College Department of Internal Medicine Department of Radiation Oncology Department of Medical Oncology, Shantou Central Hospital, Shantou, China.
Medicine (Baltimore). 2018 Jul;97(30):e11569. doi: 10.1097/MD.0000000000011569.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line treatment for nonsmall-cell lung cancer (NSCLC) patients with an activating EGFR mutation. Osimertinib, compared with erlotinib or gefitinib, showed an improvement in progression-free survival (PFS) in a recent trial. The authors compared EGFR TKIs in terms of PFS in a network meta-analysis.
The PubMed and Embase databases and meeting abstracts were screened for relevant studies between January 2009 and November 2017. A random-effect frequentist network meta-analysis model was conducted to assess PFS. P-score was used to rank treatment effects.
Eleven trials with 3145 patients and 5 TKIs (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) were included. Heterogeneity and inconsistency existed in the network analysis. Gefitinib and erlotinib had similar effects (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.76-1.15). For all patients, the 3 TKIs with the highest probability of benefit were osimertinib, dacomitinib, and afatinib, with P-scores of 91%, 78%, and 46%, respectively. Compared with erlotinib or gefitinib, osimertinib was associated with improvement in men (HR = 0.79, 95% CI, 0.68-0.92), non-Asians (HR = 0.63, 95% CI, 0.40-0.98), smokers (HR = 0.73, 95% CI, 0.56-0.95), and those with a Del19 mutation (HR = 0.69, 95% CI, 0.54-0.90); dacomitinib and afatinib showed no improvement. Toxicity profiles mostly overlapped in all the EGFR TKIs. Toxicity-related death was rare.
Osimertinib was shown to be the best agent to achieve the longest PFS in NSCLC patients with an activating EGFR mutation. However, the benefit of osimertinib might be restricted to certain subgroups.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）是具有激活型EGFR突变的非小细胞肺癌（NSCLC）患者的首选一线治疗药物。在最近一项试验中，与厄洛替尼或吉非替尼相比，奥希替尼在无进展生存期（PFS）方面有所改善。作者在一项网状Meta分析中比较了EGFR TKIs在PFS方面的情况。
检索PubMed和Embase数据库以及会议摘要，查找2009年1月至2017年11月期间的相关研究。采用随机效应频率学派网状Meta分析模型评估PFS。使用P值对治疗效果进行排序。
纳入了11项试验，共3145例患者，涉及5种TKIs（吉非替尼、厄洛替尼、阿法替尼、达可替尼和奥希替尼）。网状分析中存在异质性和不一致性。吉非替尼和厄洛替尼效果相似（风险比[HR] 0.94，95%置信区间[CI] 0.76 - 1.15）。对于所有患者，获益可能性最高的3种TKIs是奥希替尼、达可替尼和阿法替尼，P值分别为91%、78%和46%。与厄洛替尼或吉非替尼相比，奥希替尼在男性（HR = 0.79，95% CI，0.68 - 0.92）、非亚洲人（HR = 0.63，95% CI，0.40 - 0.98）、吸烟者（HR = 0.73，95% CI，0.56 - 0.95）以及具有Del19突变的患者（HR = 0.69，95% CI，0.54 - 0.90）中与PFS改善相关；达可替尼和阿法替尼未显示出改善。所有EGFR TKIs的毒性特征大多重叠。与毒性相关的死亡罕见。
奥希替尼被证明是在具有激活型EGFR突变的NSCLC患者中实现最长PFS的最佳药物。然而，奥希替尼的获益可能仅限于某些亚组。
