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贝伐珠单抗联合不同铂类双药方案一线治疗晚期非鳞状非小细胞肺癌的网状meta 分析。

Bevacizumab in combination with different platinum-based doublets in the first-line treatment for advanced nonsquamous non-small-cell lung cancer: A network meta-analysis.

机构信息

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.

State Key Laboratory of Oncology in South China, Guangzhou, China.

出版信息

Int J Cancer. 2018 Apr 15;142(8):1676-1688. doi: 10.1002/ijc.31175. Epub 2017 Dec 4.

Abstract

Platinum-based doublet chemotherapy with or without bevacizumab is the standard treatment for untreated advanced nonsquamous non-small-cell lung cancer (NS-NSCLC). However, adding bevacizumab to chemotherapies other than paclitaxel-carboplatin is, though widely applied clinically, largely unjustified due to the lack of head-to-head data. We performed a Bayesian network meta-analysis (NMA) to address this important issue. Data of 8,548 patients from 18 randomized controlled trials (RCTs) receiving six treatments, including taxane-platinum (Taxane-Pt), gemcitabine-platinum (Gem-Pt), pemetrexed-platinum (Pem-Pt), taxane-platinum + bevacizumab (Taxane-Pt + B), gemcitabine-platinum + bevacizumab (Gem-Pt + B) and pemetrexed-platinum + bevacizumab (Pem-Pt + B), were incorporated into the analyses. Direct and indirect evidence of overall survival (OS) and progression-free survival (PFS) were synthesized at the hazard ratio (HR) scale and evidence of objective response rate (ORR) and serious adverse events (SAE) were synthesized at the odds ratio (OR) scale. Taxane-Pt + B showed significant advantages in OS (HR = 0.79, p < 0.001), PFS (HR = 0.54, p < 0.001) and ORR (OR = 2.7, p < 0.001) over Taxane-Pt with comparable tolerability (OR = 3.1, p = 0.08). Gem-Pt + B showed no OS benefit compared to any other treatment. No significant differences were detected between Pem-Pt + B and Pem-Pt in four outcomes. In terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt + B were ranked the first and second, respectively. In conclusion, in the first-line treatment for advanced NS-NSCLC, Taxane-Pt and Gem-Pt are the most and least preferable regimens to be used with bevacizumab, respectively. Adding bevacizumab to Pem-Pt remains unjustified because it fails to improve efficacy or tolerability. In terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt + B are the best and second-best treatment for this population.

摘要

顺铂为基础的双联化疗联合或不联合贝伐珠单抗是未经治疗的晚期非鳞状非小细胞肺癌(NS-NSCLC)的标准治疗方法。然而,将贝伐珠单抗添加到紫杉醇-卡铂以外的化疗药物中,尽管在临床上广泛应用,但由于缺乏头对头数据,在很大程度上是没有依据的。我们进行了一项贝叶斯网络荟萃分析(NMA)来解决这个重要问题。我们纳入了来自 18 项随机对照试验(RCTs)的 8548 名患者的数据,这些患者接受了六种治疗方法,包括紫杉醇-顺铂(Taxane-Pt)、吉西他滨-顺铂(Gem-Pt)、培美曲塞-顺铂(Pem-Pt)、紫杉醇-顺铂+贝伐珠单抗(Taxane-Pt+B)、吉西他滨-顺铂+贝伐珠单抗(Gem-Pt+B)和培美曲塞-顺铂+贝伐珠单抗(Pem-Pt+B)。我们将总生存期(OS)和无进展生存期(PFS)的直接和间接证据综合在风险比(HR)尺度上,将客观缓解率(ORR)和严重不良事件(SAE)的证据综合在优势比(OR)尺度上。与 Taxane-Pt 相比,Taxane-Pt+B 在 OS(HR=0.79,p<0.001)、PFS(HR=0.54,p<0.001)和 ORR(OR=2.7,p<0.001)方面具有显著优势,且耐受性相当(OR=3.1,p=0.08)。与其他治疗方法相比,Gem-Pt+B 并未显示出 OS 获益。在四个结局中,Pem-Pt+B 与 Pem-Pt 之间未检测到显著差异。就获益-风险比而言,Pem-Pt 和 Taxane-Pt+B 分别排名第一和第二。总之,在晚期 NS-NSCLC 的一线治疗中,Taxane-Pt 和 Gem-Pt 分别是最适合和最不适合与贝伐珠单抗联合使用的方案。在 Pem-Pt 中添加贝伐珠单抗仍然没有依据,因为它不能提高疗效或耐受性。就获益-风险比而言,Pem-Pt 和 Taxane-Pt+B 是该人群的最佳和第二佳治疗选择。

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