Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. The degree of HER2 ov...Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. The degree of HER2 overexpression and amplification varies with the location of the carcinoma, with higher expression in the gastroesophageal and proximal parts compared to the distal parts of the stomach. Further, HER2 overexpression and amplification also seems to be related to the Lauren histological classification, with higher levels found in the intestinal phenotype compared to the diffuse and mixed types. The prognostic properties of HER2 overexpression and amplification are still under debate, but a large number of studies seem to indicate that HER2 is a negative prognostic factor. The usefulness of HER2 targeted therapy in gastric cancer was demonstrated in the ToGA trial, where HER2-positive patients with advanced gastric and gastroesophageal junction adenocarcinoma were randomized to receive 5-FU/capecitabine and cisplatin, either alone or in combination with trastuzumab. A statically significant gain in overall survival was seen in patients who received the combined treatment of trastuzumab and chemotherapy. Patients with a strong overexpression of the HER2 protein (IHC3+) specifically benefited from the treatment, with a median overall survival of 17.9 mo. As a consequence of the positive results of the ToGA trial, patients with advanced gastric or gastroesophageal junction adenocarcinoma are now routinely tested for HER2. The ToGA trial must be characterized as a landmark in the treatment of gastric cancer and it has paved the way for a number of new HER2 targeted compounds such as pertuzumab, ado-trastuzumab emtansine, lapatinib, afatinib, and dacomitinib, which are currently undergoing phase II and III clinical testing. Overall, this review will discuss the current status of HER2 in gastric and gastroesophageal junction cancer and the future direction in relation to HER2 target therapy.展开更多
目的:系统评价曲妥珠单抗共轭复合物(ado-trastuzumab emtansine,T-DM1)不良反应的发生率。方法:检索Pub Med、Clinicaltrials.gov和CNKI数据库,收集2015年2月前发表的T-DM1临床研究,采用Rev Man 5.3软件分析。结果:共纳入3项随机对照试...目的:系统评价曲妥珠单抗共轭复合物(ado-trastuzumab emtansine,T-DM1)不良反应的发生率。方法:检索Pub Med、Clinicaltrials.gov和CNKI数据库,收集2015年2月前发表的T-DM1临床研究,采用Rev Man 5.3软件分析。结果:共纳入3项随机对照试验,共计1700例患者。Meta分析结果显示,所有程度不良反应发生率:T-DM1组血小板减少的发生率高于对照组[RR=6.76,95%CI(3.47,13.17),P=0.12,I^2=53%];T-DM1组AST升高的发生率高于对照组[RR=2.68,95%CI(1.40,5.14),P=0.04,I^2=69%];T-DM1组中性粒细胞减少的发生率低于对照组[RR=0.35,95%CI(0.18,0.71),P=0.003,I^2=83%];T-DM1组腹泻的发生率低于对照组[RR=0.34,95%CI(0.25,0.47),P=0.12,I^2=52%];两组贫血的发生率差异无统计学意义[RR=0.87,95%CI(0.51,1.49),P=0.05,I^2=66%]。3-4度不良反应发生率:T-DM1组中性粒细胞减少的发生率低于对照组[RR=0.20,95%CI(0.08,0.50),P=0.02,I^2=75%];T-DM1组腹泻的发生率低于对照组[RR=0.10,95%CI(0.05,0.18),P=0.53,I^2=0%];两组血小板减少的发生率差异无统计学意义[RR=6.93,95%CI(0.80,59.80),P=0.004,I^2=82%];两组贫血的发生率差异无统计学意义[RR=1.21,95%CI(0.65,2.26),P=0.59,I^2=0%];两组AST升高的发生率差异无统计学意义[RR=3.13,95%CI(0.77,12.70),P=0.07,I^2=63%]。结论:与传统化疗方案相比,T-DM1具有良好的安全性。展开更多
文摘Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. The degree of HER2 overexpression and amplification varies with the location of the carcinoma, with higher expression in the gastroesophageal and proximal parts compared to the distal parts of the stomach. Further, HER2 overexpression and amplification also seems to be related to the Lauren histological classification, with higher levels found in the intestinal phenotype compared to the diffuse and mixed types. The prognostic properties of HER2 overexpression and amplification are still under debate, but a large number of studies seem to indicate that HER2 is a negative prognostic factor. The usefulness of HER2 targeted therapy in gastric cancer was demonstrated in the ToGA trial, where HER2-positive patients with advanced gastric and gastroesophageal junction adenocarcinoma were randomized to receive 5-FU/capecitabine and cisplatin, either alone or in combination with trastuzumab. A statically significant gain in overall survival was seen in patients who received the combined treatment of trastuzumab and chemotherapy. Patients with a strong overexpression of the HER2 protein (IHC3+) specifically benefited from the treatment, with a median overall survival of 17.9 mo. As a consequence of the positive results of the ToGA trial, patients with advanced gastric or gastroesophageal junction adenocarcinoma are now routinely tested for HER2. The ToGA trial must be characterized as a landmark in the treatment of gastric cancer and it has paved the way for a number of new HER2 targeted compounds such as pertuzumab, ado-trastuzumab emtansine, lapatinib, afatinib, and dacomitinib, which are currently undergoing phase II and III clinical testing. Overall, this review will discuss the current status of HER2 in gastric and gastroesophageal junction cancer and the future direction in relation to HER2 target therapy.
文摘目的:系统评价曲妥珠单抗共轭复合物(ado-trastuzumab emtansine,T-DM1)不良反应的发生率。方法:检索Pub Med、Clinicaltrials.gov和CNKI数据库,收集2015年2月前发表的T-DM1临床研究,采用Rev Man 5.3软件分析。结果:共纳入3项随机对照试验,共计1700例患者。Meta分析结果显示,所有程度不良反应发生率:T-DM1组血小板减少的发生率高于对照组[RR=6.76,95%CI(3.47,13.17),P=0.12,I^2=53%];T-DM1组AST升高的发生率高于对照组[RR=2.68,95%CI(1.40,5.14),P=0.04,I^2=69%];T-DM1组中性粒细胞减少的发生率低于对照组[RR=0.35,95%CI(0.18,0.71),P=0.003,I^2=83%];T-DM1组腹泻的发生率低于对照组[RR=0.34,95%CI(0.25,0.47),P=0.12,I^2=52%];两组贫血的发生率差异无统计学意义[RR=0.87,95%CI(0.51,1.49),P=0.05,I^2=66%]。3-4度不良反应发生率:T-DM1组中性粒细胞减少的发生率低于对照组[RR=0.20,95%CI(0.08,0.50),P=0.02,I^2=75%];T-DM1组腹泻的发生率低于对照组[RR=0.10,95%CI(0.05,0.18),P=0.53,I^2=0%];两组血小板减少的发生率差异无统计学意义[RR=6.93,95%CI(0.80,59.80),P=0.004,I^2=82%];两组贫血的发生率差异无统计学意义[RR=1.21,95%CI(0.65,2.26),P=0.59,I^2=0%];两组AST升高的发生率差异无统计学意义[RR=3.13,95%CI(0.77,12.70),P=0.07,I^2=63%]。结论:与传统化疗方案相比,T-DM1具有良好的安全性。
