Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Int J Cancer. 2018 Jul 15;143(2):438-448. doi: 10.1002/ijc.31325. Epub 2018 Mar 14.
According to the Trastuzumab for Gastric Cancer (ToGA) study, trastuzumab plus cisplatin and capecitabine/5-fluorouracil (5-FU) is standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced oesophagogastric cancer. We examined the relative efficacy and safety of alternative trastuzumab-based cytotoxic backbone regimens compared to the standard ToGA regimen using meta-analysis. We searched Medline, EMBASE, CENTRAL and ASCO and ESMO up to March 2017 for studies investigating alternative first-line trastuzumab-based regimens for HER2-positive oesophagogastric cancer, defined as high protein expression IHC3+ or IHC2+ and gene amplification by in situ hybridisation. We compared primary outcome overall survival (OS) of alternative trastuzumab-based regimens to the ToGA regimen. Hazard ratios (HRs) and 95% confidence intervals (95%CI) were calculated by extraction of the published Kaplan-Meier curves. Incidence counts and toxicity sample-sizes were extracted for adverse events and compared using single-arm proportion meta-analysis in R. Fifteen studies (N = 557 patients) were included. OS was significantly longer with regimen trastuzumab plus doublet oxaliplatin and capecitabine/5-FU (median OS = 20.7 months) versus ToGA (16.0 months, HR = 0.75, 95% CI = 0.59-0.99) and was less toxic. Trastuzumab plus doublet cisplatin and S-1 showed no OS difference versus ToGA, but showed a different toxicity profile, including less hand-foot syndrome. Trastuzumab plus cisplatin or capecitabine as singlet backbone showed significantly worse survival and more toxicity versus ToGA regimen. Trastuzumab with triplet cytotoxic backbones or with bevacizumab and doublet cytotoxic backbone showed no survival benefit and more toxicity. In conclusion, trastuzumab plus doublet cytotoxic backbone containing oxaliplatin is preferable over the ToGA regimen with cisplatin. S-1 can substitute capecitabine or 5-FU when specific toxicities are encountered.
根据曲妥珠单抗治疗胃癌（ToGA）研究，曲妥珠单抗联合顺铂和卡培他滨/5-氟尿嘧啶（5-FU）是治疗人表皮生长因子受体 2（HER2）阳性晚期胃食管交界癌的标准一线治疗方法。我们使用荟萃分析研究了替代曲妥珠单抗为基础的细胞毒性骨干方案与标准 ToGA 方案相比的相对疗效和安全性。我们检索了 Medline、EMBASE、CENTRAL 和 ASCO 以及 ESMO，截至 2017 年 3 月，研究了替代曲妥珠单抗为基础的一线治疗方案，用于 HER2 阳性胃食管交界癌，定义为高蛋白表达 IHC3+或 IHC2+和原位杂交基因扩增。我们比较了替代曲妥珠单抗为基础的方案与 ToGA 方案的主要结局总生存（OS）。通过提取已发表的 Kaplan-Meier 曲线计算危险比（HR）和 95%置信区间（95%CI）。通过在 R 中使用单臂比例荟萃分析提取不良反应的发生率计数和毒性样本大小，并进行比较。纳入了 15 项研究（N=557 例患者）。曲妥珠单抗联合奥沙利铂和卡培他滨/5-FU 方案（中位 OS=20.7 个月）的 OS 明显长于 ToGA 方案（16.0 个月，HR=0.75，95%CI=0.59-0.99），且毒性更小。曲妥珠单抗联合顺铂和 S-1 与 ToGA 方案相比，OS 无差异，但毒性谱不同，包括手足综合征较少。曲妥珠单抗联合顺铂或卡培他滨作为单一骨干方案与 ToGA 方案相比，生存显著较差，毒性更大。曲妥珠单抗联合三药细胞毒性骨干方案或联合贝伐单抗和二药细胞毒性骨干方案无生存获益，毒性更大。总之，曲妥珠单抗联合含奥沙利铂的二药细胞毒性骨干方案优于含顺铂的 ToGA 方案。当出现特定毒性时，S-1 可替代卡培他滨或 5-FU。
