中国循证医学杂志

中国循证医学杂志

一代表皮生长因子酪氨酸激酶受体抑制剂与培美曲塞比较二线治疗晚期非小细胞肺癌的疗效及安全性的 Meta 分析

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目的系统评价一代表皮生长因子酪氨酸激酶受体抑制剂(EGFR-TKI)与培美曲塞比较二线治疗晚期非小细胞肺癌(NSCLC)的疗效和安全性。方法计算机检索 PubMed、EMbase、The Cochrane Library、CNKI、WanFang Data 和 CBM 数据库,搜集关于一代 EGFR-TKI 与培美曲塞二线治疗晚期 NSCLC 的 RCT,检索时限均从建库至 2017 年 6 月。由 2 名研究者独立筛选文献、提取资料和评价纳入研究的偏倚风险后,采用 RevMan 5.3 软件进行 Meta 分析。结果最终纳入 20 个 RCT,包括 2 242 例患者。Meta 分析结果显示:一代 EGFR-TKI 组在无进展生存率方面明显优于培美曲塞组[HR=0.78,95%CI(0.58,0.99),P<0.000 1];但两组在完全缓解率[RR=1.81,95%CI(0.65,5.07),P=0.26]、部分缓解率[RR=0.93,95%CI(0.78,1.11),P=0.44]、疾病稳定率[RR=0.92,95%CI(0.82,1.03),P=0.16]、疾病进展率[RR=1.09,95%CI(0.99,1.20),P=0.09]、总有效率[RR=0.97,95%CI(0.72,1.30),P=0.84]、疾病控制率[RR=0.93,95%CI(0.87,1.01),P=0.07]及总生存率[HR=0.89,95%CI(0.74,1.04),P<0.572]上,差异均无统计学意义。在安全性方面,一代 EGFR-TKI 组的皮疹发生率[RR=12.43,95%CI(3.98,38.84),P<0.01]和腹泻发生率[RR=3.94,95%CI(2.32,6.70),P<0.01]明显高于培美曲塞组,而白细胞减少[RR=0.19,95%CI(0.09,0.41),P<0.01]、贫血[RR=0.40,95%CI(0.17,0.92),P=0.03]、血小板减少[RR=0.37,95%CI(0.14,0.97),P=0.04]、恶心呕吐[RR=0.50,95%CI(0.28,0.87),P=0.01]、便秘[RR=0.30,95%CI(0.14,0.64),P=0.002]均明显低于培美曲塞组。结论一代 EGFR-TKI 在二线治疗晚期 NSCLC 较培美曲塞有一定优势,可作为二线治疗 NSCLC 的常规药物之一。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。

ObjectivesTo systematically review the efficacy and safety of the first generation EGFR-TKIs versus pemetrexed as second-line treatment for advanced non-small cell lung cancer (NSCLC).MethodsDatabases including PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and CBM were searched to collect randomized controlled trials (RCTs) about the first generation EGFR-TKIs versus pemetrexed as second-line treatment for advanced NSCLC from inception to June 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 20 RCTs involving 2 242 patients were finally included. The results of meta-analysis showed that: the rate of progression free survival (PFS) in the EGFR-TKI group was superior to the pemetrexed group (HR=0.78, 95%CI 0.58 to 0.99, P<0.000 1) with significant difference. However, there was no significant difference between two groups in complete remission rate (RR=1.81, 95%CI 0.65 to 5.07,P=0.26), partial remission rate (RR=0.93, 95%CI 0.78 to 1.11, P=0.44), stable disease rate (RR=0.92, 95%CI 0.82 to 1.03, P=0.16), progression disease rate (RR=1.09, 95%CI 0.99 to 1.20, P=0.09), overall response rate (RR=0.97, 95%CI 0.72 to 1.30, P=0.84), disease control rate (RR=0.93, 95%CI 0.87 to 1.01, P=0.07) and overall survival rate (HR=0.89, 95%CI 0.74 to 1.04, P<0.572). The incidences of skin rash (RR=12.43, 95%CI 3.98 to 38.84,P<0.01) and diarrhea (RR=3.94, 95%CI 2.32 to 6.70,P<0.01) were significantly higher in the EGFR-TKI group, but the incidences of leukopenia (RR=0.19, 95%CI 0.09 to 0.41,P<0.01 ), anemia (RR=0.40, 95%CI 0.17 to 0.92,P=0.03), thrombocytopenia (RR=0.37, 95%CI 0.14 to 0.97, P=0.04), nausea and vomiting (RR=0.50, 95%CI 0.28 to 0.87, P=0.01), constipation (RR=0.30, 95%CI 0.14 to 0.64, P=0.002) were significant lower in the EGFR-TKI group than that of the pemetrexed group.ConclusionGefitinib shows some superiority to pemetrexed in second-line treatment for NSCLC, and it can be used as the second-line drug for advanced NSCLC. Due to the limited quality and quantity of included studies, more high quality studies are needed to verify the above conclusion.

关键词: 吉非替尼; 厄洛替尼; 埃克替尼; 培美曲塞; 非小细胞肺癌; 系统评价; Meta 分析; 随机对照试验

Key words: Gefitinib; Erlotinib; Icotinib; Pemetrexed; Non-small cell lung cancer; Systematic review; Meta-analysis; Randomized controlled trial

引用本文: 程相松, 刘海洋, 宋永安, 徐志伟, 张晓菊. 一代表皮生长因子酪氨酸激酶受体抑制剂与培美曲塞比较二线治疗晚期非小细胞肺癌的疗效及安全性的 Meta 分析. 中国循证医学杂志, 2018, 18(4): 326-332. doi: 10.7507/1672-2531.201708048 复制

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