Gefitinib Plus Chemotherapy Versus Cetuximab Plus Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer: A Network Meta-Analysis

Heng Shi, Zheng Liu, Babo Zhang, Shuaifei Ji
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Abstract

Recent randomized control trials have revealed the efficacy and safety of gefitinib plus chemotherapy and cetuximab plus chemotherapy on the treatment of advanced non-small cell lung cancer, but little is known about the differences between them lacking of direct evidences. Randomized control trials were selected by formal search of electronic databases (PubMed, Embase, and Cochrane Library) and trials registers on the Internet. This systematic review and meta-analysis is reported in accordance with the Preferred Items for Systematic Reviews and Meta-analysis (PRISMA) Statement and was registered at International Prospective Register of Systematic Reviews. 14 trails were identified finally, with 8 studies about gefitinib plus chemotherapy vs chemotherapy alone and 6 studies about cetuximab plus chemotherapy plus vs chemotherapy alone. For overall survival and progression-free survival, the relative HRs of gefitinib plus chemotherapy vs cetuximab plus chemotherapy were 0.96 (0.81-1.13, p=0.583) and 0.69 (0.45-1.05, p=0.080) on first-line treatment and 1.60 (1.01-2.54, p=0.044) and 0.83 (0.61-1.15, p=0.267) on second-line treatment. For objective response rate and one-year survival rate on first-line treatment, the relative RRs of gefitinib plus chemotherapy vs cetuximab plus chemotherapy were 0.89 (0.69-1.15, p=0.395) and 0.84 (0.72-0.98, p=0.026). For adverse events, the risk of relative RR of leukopenia all grades was 0.73 (0.58-0.91, p=0.006), while other events didn’t exhibit significant differences. Subgroup analysis found that comparing to cetuximab plus chemotherapy, gefitinib plus chemotherapy appeared a better improvement in one-year survival rate of USA advanced NSCLC population [RR=0.83 (0.70-0.99, p=0.042)]. It concluded that, on the treatment of advanced NSCLC patients, the efficacy and safety of gefitinib plus chemotherapy are superior to cetuximab plus chemotherapy on first-line treatment, while the latter may be a better choice as well when it occurs to second-line treatment.
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吉非替尼联合化疗与西妥昔单抗联合化疗治疗晚期非小细胞肺癌:网络荟萃分析
近期的随机对照试验显示吉非替尼联合化疗和西妥昔单抗联合化疗治疗晚期非小细胞肺癌的疗效和安全性,但缺乏直接证据,对两者之间的差异知之甚少。随机对照试验通过正式检索电子数据库(PubMed、Embase和Cochrane Library)和因特网上的试验注册库来选择。该系统评价和荟萃分析按照系统评价和荟萃分析(PRISMA)声明的首选项目进行报道,并在国际前瞻性系统评价注册中注册。最终确定了14项试验,其中8项研究是关于吉非替尼加化疗vs单独化疗,6项研究是关于西妥昔单抗加化疗vs单独化疗。对于总生存期和无进展生存期,吉非替尼加化疗vs西图昔单抗加化疗的相对hr在一线治疗组分别为0.96 (0.81-1.13,p=0.583)和0.69 (0.45-1.05,p=0.080),二线治疗组分别为1.60 (1.01-2.54,p=0.044)和0.83 (0.61-1.15,p=0.267)。在一线治疗的客观缓解率和1年生存率方面,吉非替尼联合化疗与西妥昔单抗联合化疗的相对相对危险度分别为0.89 (0.69-1.15,p=0.395)和0.84 (0.72-0.98,p=0.026)。不良事件方面,各级别白细胞减少的相对RR风险为0.73 (0.58 ~ 0.91,p=0.006),其他事件差异无统计学意义。亚组分析发现,与西妥昔单抗联合化疗相比,吉非替尼联合化疗对美国晚期NSCLC患者的1年生存率有更好的改善[RR=0.83 (0.70-0.99, p=0.042)]。综上所述,对于晚期NSCLC患者,吉非替尼联合化疗在一线治疗的疗效和安全性优于西妥昔单抗联合化疗,而在二线治疗时,西妥昔单抗也可能是更好的选择。
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