关键词： ADME, absorption, distribution, metabolism, and excretion Ab, monoclonal antibody BSC, best supportive care CHT, chemotherapy EGFR, epidermal growth factor receptor GC, gastric cancer HER2, human epidermal growth factor receptor 2 HER3, human epidermal growth factor receptor 3 MET, mesenchymal epithelial transition factor NGS, next generation sequencing NSCLC, non-small cell lung cancer OR, odds-ratio OS, overall survival PARP, poly ADP ribose polymerase PFS, progression free survival PI3K, phosphatidylinositide 3-kinases PRISMA, preferred reporting items for systematic reviews and meta-analyses RAF, rapidly accelerated fibrosarcoma RAS, rat sarcoma viral oncogene homolog RCTs, randomized clinical trials RR, response rate TKI, tyrosine kinase inhibitor VEGF, vascular endothelial growth factor VEGFR: VEGF receptor aGC, advanced gastric cancer angiogenesis gastric cancer mTOR, mammalian target of rapamycin mTORC, mTOR complex meta-analysis randomized clinical trials systemic chemotherapy targeted pathways targeted therapy

Mesh ： Angiogenesis Inhibitors / therapeutic use Antineoplastic Combined Chemotherapy Protocols / adverse effects therapeutic use ErbB Receptors / antagonists & inhibitors Humans Molecular Targeted Therapy / methods Randomized Controlled Trials as Topic Receptor, ErbB-2 / antagonists & inhibitors Stomach Neoplasms / drug therapy epidemiology mortality Survival Analysis

来  源：   DOI：10.1080/15384047.2015.1056415   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
It is still uncertain if targeted therapy-based regimens in advanced gastric cancer actually produce survival benefit. To shed light on this important question, we performed a systematic review and meta-analyses on each relevant targeted-pathway. By searching literature databases and proceedings of major cancer meetings in the time-frame 2005-2014, 22 randomized clinical trials exploring targeted therapy for a total of 7022 advanced gastric cancer patients were selected and included in the final analysis. Benefit was demonstrated for antiangiogenic agents in terms of overall survival (HR 0.759; 95%CI 0.655-0.880; p < 0.001). Conversely no benefit was found for EGFR pathway (HR 1.077; 95%CI 0.847-1.370; p = 0.543). Meta-analysis of HER-2 pathway confirmed improvement in terms of survival outcome, already known for this class of drugs (HR 0.823; 95%CI 0.722-0.939; p = 0.004). Pooled analysis demonstrated a significant survival benefit (OS: HR 0.823; PFS: HR 0.762) with acceptable tolerability profile for targeted-based therapies as compared to conventional treatments. This finding conflicts with the outcome of most individual studies, probably due to poor trial design or patients selection. In conclusion, our findings demonstrate a significant survival benefit for targeted therapy in its whole, which can be ascribed to anti-angiogenic and anti-HER2 agents.
摘要：
目前尚不确定靶向治疗为基础的方案是否真的在晚期胃癌中产生生存益处。为了阐明这个重要的问题，我们对每个相关的靶向途径进行了系统综述和荟萃分析.通过检索2005-2014年主要癌症会议的文献数据库和会议记录，选择了22项探索靶向治疗的随机临床试验，共7022例晚期胃癌患者，并纳入最终分析。在总生存期方面，抗血管生成药物的获益得到证实(HR0.759;95CI0.655-0.880;p<0.001)。相反，EGFR通路没有发现益处（HR1.077;95CI0.847-1.370;p=0.543）。HER-2通路的Meta分析证实了在生存结局方面的改善，已知这类药物(HR0.823;95CI0.722-0.939;p=0.004)。与常规治疗相比，汇总分析显示了显着的生存益处（OS：HR0.823；PFS：HR0.762），靶向治疗具有可接受的耐受性。这一发现与大多数个体研究的结果相冲突，可能是由于不良的试验设计或患者选择。总之,我们的研究结果表明，靶向治疗在整体上具有显著的生存益处，这可以归因于抗血管生成和抗HER2药物。
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