摘要
背景与目的化疗与表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)联合疗法一直是许多研究的焦点,其中间插联合疗法受到了更多研究者的关注。本研究旨在系统评价化疗与EGFR-TKIs间插联合疗法对比单独化疗一线治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的有效性及安全性。方法检索The Cochrane Library、PubM ed、EMBASE、中国生物医学文献数据库(CBM)、知网和万方等数据库关于化疗间插联合EGFR-TKIs疗法和单独化疗一线治疗晚期NSCLC的随机对照试验(randomized controlled trial,RCT),分析如下结局指标:无进展生存期(progression-free survival,PFS)、总体生存期(overall survival,OS)、客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)以及不良反应发生率。由两名研究者根据Cochrane系统评价手册筛选文献、进行质量评价以及提取并交叉核对数据。应用Stata12.0软件进行meta分析。结果本研究共纳入6个RCT,共计933例晚期NSCLC患者。Meta分析结果表明,在晚期NSCLC患者一线治疗中,与单独化疗相比,间插联合疗法虽然延长了患者的PFS(HR=0.72,95%CI:0.53-0.98,P=0.037),但并不能提高其OS(HR=0.85,95%CI:0.72-1.01,P=0.060)、ORR(OR=1.59,95%CI:0.86-2.95,P=0.142)和DCR(OR=1.09,95%CI:0.95-1.25,P=0.226)。进一步的亚组分析发现,间插联合疗法提高了女性、腺癌、从不吸烟和EGFR突变等患者的PFS,差异具有统计学意义。在安全性方面,间插联合疗法的主要不良反应为皮疹(OR=7.81,95%CI:3.74-16.34,P<0.001)和腹泻(OR=2.73,95%CI:1.92-3.89,P<0.001)。结论一线接受化疗间插联合EGFR-TKIs治疗的NSCLC患者的PFS明显高于接受单独化疗者,其主要不良事件是皮疹和腹泻。因此,间插联合治疗具有一定优势,但仍需要更多大样本、高质量的RCT进一步验证。
Background and objective The combination therapy of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） has attracted the attention of more and more investigators. The aim of this meta-analysis is to evaluate the clinical efficacy and safety of intercalated combination of chemotherapy and EGFR- TKIs versus chemotherapy alone in the first-line therapy of advanced non-small cell lung cancer （NSCLC）. Methods We retrieved the Co- chrane Library, PubMed, EMBASE, CBM, CNKI and Wanfang databases for randomized controlled trials which involved the intercalated combination of chemotherapy and EGFR-TKIs, and chemotherapy alone in the first-line treatment of advanced NSCLC. The progression-free survival （PFS）, overall survival （OS）, objective response rate （ORR）, disease control rate （DCR）, and adverse events were analyzed. The quality evaluation and cross-checked data were independently performed by two in- vestigators according to the Cochrane Systematic Reviews Handbook. The Stata 12.0 software was used to conduct the meta- analysis. Results This study included 933 NSCLC patients from 6 RCTs. The rneta-analysis demonstrated that the intercalated combination of chemotherapy and EGFR-TKIs significantly prolonged the PFS （HR=0.72, 95%CI： 0.53-0.98, P=0.037） of advanced NSCLC patients compared with mono-chemotherapy. However, there was no statistical difference in OS （HR=0.85, 95%CI： 0.72-1.01, P=0.060）, ORR （OR=1.59, 95%CI： 0.86-2.95, P=0.142） and DCR （OR= 1.09, 95%CI： 0.95-1.25, P=0.226） between the two groups. Further, the subgroup analysis showed that the intercalated combination markedly improved the PFS in female, adenocarcinoma, never smoking, EGFR mutant patients. In the aspect of safety, the main side effects of the interca- lated combination therapy were rash （OR=7.81, 95%CI： 3.74-16.34, P〈0.001） and diarrhea （OR=2.73, 95%CI： 1.92-3.89, P〈0.001）. Conclusion The intercalated combination of chemotherapy and EGFR-TKIs significantly prolonged the PFS in the first-line therapy of advanced NSCLC patients compared with mono-chemotherapy, and the main adverse events were toler- able rash and diarrhea. Together, the intercalated combination shows promising results, and more large-scale and high-quality RCTs are still needed.
出处
《中国肺癌杂志》
CAS
CSCD
北大核心
2016年第12期837-846,共10页
Chinese Journal of Lung Cancer
基金
江西省科技支撑计划项目(No.20121BBG70053)资助~~
关键词
肺肿瘤
化疗
表皮生长因子受体酪氨酸激酶抑制剂
间插联合疗法
一线治疗
META分析
Lung neoplasms
Chemotherapy
Epidermal growth factor receptor-tyrosine kinase inhibitors
Inter-calated combination
First-line treatment
Meta-analysis
作者简介
梅同华，E-mail：mtonghua@163．com
