Hess Lisa M, DeLozier Amy M, Natanegara Fanni, Wang Xiaofei, Soldatenkova Victoria, Brnabic Alan, Able Stephen L, Brown Jacqueline
Eli Lilly and Company, Indianapolis, Indiana, USA.
Lilly Deutschland GmbH, Bad Homburg, Germany.
J Thorac Dis. 2018 Dec;10(12):6677-6694. doi: 10.21037/jtd.2018.11.87.
The objectives of this systematic review and meta-analysis were to compare the survival, toxicity, and quality of life of patients treated with necitumumab in combination with gemcitabine and cisplatin. These agents were investigated in published randomized controlled trials (RCTs) of patients with squamous non-small cell lung cancer (NSCLC) in the first-line setting.
The systematic review was executed on January 27, 2015, and updated on August 21, 2016, using a pre-specified search strategy. Searches were conducted using PubMed, Medline, and EMBASE, with supplemental searches using the Evidence Based Medicine Reviews and ClinicalTrials.gov to identify RCTs published in English from 1995-2016 and reporting at least one of the primary outcomes [overall survival (OS), progression-free survival (PFS), toxicity, or quality of life] in patients who received first-line treatment for advanced or metastatic squamous NSCLC. Study quality and risk of bias were assessed using the Physiotherapy Evidence Database (PEDro) scale and Cochrane risk of bias tool, respectively. A Baysian network meta-analysis was performed on the primary outcomes. Hazard ratios (HRs) were evaluated for the primary analysis; secondary analyses were conducted using median OS data. Planned sensitivity analyses were conducted including reanalysis using a Frequentist approach and limiting analyses to subsets based on clinical and demographic covariates.
The systematic literature review resulted in identification of 4,016 unique publications; 40 publications (35 unique trials) were eligible for inclusion. Eight studies connected to a common network for the OS analysis using HR data. The majority of studies were not limited to squamous NSCLC, thus analyzable data were limited to a subset of data within the published trials. Carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin were associated with lower HRs for OS versus all other comparators. Nine studies connected to the network for the PFS analysis in which necitumumab in combination with gemcitabine and cisplatin was associated with the lowest HR. Data were not available to analyze toxicity or quality of life.
Although the results suggest that carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin may have value in terms of OS versus other comparators, the results should be interpreted with caution due to the limited number of studies (with few focused exclusively on squamous NSCLC) and wide credible intervals.
本系统评价和荟萃分析的目的是比较接受奈昔妥珠单抗联合吉西他滨和顺铂治疗的患者的生存率、毒性和生活质量。这些药物在已发表的一线鳞状非小细胞肺癌（NSCLC）患者随机对照试验（RCT）中进行了研究。
系统评价于2015年1月27日进行，并于2016年8月21日更新，采用预先指定的检索策略。检索使用PubMed、Medline和EMBASE进行，并使用循证医学评论和ClinicalTrials.gov进行补充检索，以识别1995年至2016年以英文发表的RCT，并报告接受晚期或转移性鳞状NSCLC一线治疗的患者的至少一项主要结局[总生存期（OS）、无进展生存期（PFS）、毒性或生活质量]。分别使用物理治疗证据数据库（PEDro）量表和Cochrane偏倚风险工具评估研究质量和偏倚风险。对主要结局进行贝叶斯网络荟萃分析。对主要分析评估风险比（HRs）；使用中位OS数据进行次要分析。进行了计划的敏感性分析，包括使用频率学派方法重新分析以及将分析限于基于临床和人口统计学协变量的亚组。
系统文献评价共识别出4016篇独特的出版物；40篇出版物（35项独特试验）符合纳入标准。八项研究使用HR数据连接到用于OS分析的共同网络。大多数研究不限于鳞状NSCLC，因此可分析的数据限于已发表试验中的一部分数据。与所有其他对照相比，卡铂+S-1以及奈昔妥珠单抗联合吉西他滨和顺铂与较低的OS HR相关。九项研究连接到用于PFS分析的网络，其中奈昔妥珠单抗联合吉西他滨和顺铂与最低的HR相关。没有可用于分析毒性或生活质量的数据。
尽管结果表明，与其他对照相比，卡铂+S-1以及奈昔妥珠单抗联合吉西他滨和顺铂在OS方面可能具有价值，但由于研究数量有限（很少专门针对鳞状NSCLC）且可信区间较宽，结果应谨慎解释。
