目的评价抗体药物偶联物(ADC)类药物治疗乳腺癌的疗效和安全性,为临床用药提供循证依据。方法计算机检索中国知网、万方数据库、维普网、PubMed、the Cochrane Library、Embase、Web of Science,收集恩美曲妥珠单抗、德曲妥珠单抗和戈...目的评价抗体药物偶联物(ADC)类药物治疗乳腺癌的疗效和安全性,为临床用药提供循证依据。方法计算机检索中国知网、万方数据库、维普网、PubMed、the Cochrane Library、Embase、Web of Science,收集恩美曲妥珠单抗、德曲妥珠单抗和戈沙妥珠单抗(试验组)对比化疗药物或其他抗肿瘤药物(对照组)的随机对照试验(RCT),检索时限为建库起至2023年4月。筛选文献,提取资料并评价文献质量后,采用RevMan 5.4.1软件进行Meta分析。结果共纳入8项RCT,共计5577例患者。Meta分析结果显示,试验组患者的无进展生存期(PFS)[HR=0.76,95%CI(0.69,0.83),P<0.00001]、总生存期(OS)[HR=0.87,95%CI(0.81,0.93),P<0.0001]、临床获益率(CBR)[OR=2.70,95%CI(1.15,6.33),P=0.02]均显著长于/高于对照组;两组患者的客观缓解率(ORR)比较,差异无统计学意义[OR=2.34,95%CI(0.59,9.33),P=0.23]。亚组分析结果显示,试验组人表皮生长因子受体-2(HER2)阳性、HER2阴性患者的PFS以及HER2阳性患者的OS均显著高于对照组(P<0.05)。试验组患者的贫血、天冬氨酸转氨酶升高发生率均显著高于对照组(P<0.05)。敏感性分析结果显示,以PFS、OS、ORR为指标时,所得结果较稳健;以CBR为指标时,所得结果缺乏稳健性。结论ADC类药物用于乳腺癌的疗效显著,但会增加贫血和天冬氨酸转氨酶升高的发生风险。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
Amplification of the human epidermal growth factor receptor 2(HER2)gene and overexpression of the HER2protein is found in 15%-20%of patients with gastric and gastroesophageal junction cancer.The degree of HER2 overexp...Amplification of the human epidermal growth factor receptor 2(HER2)gene and overexpression of the HER2protein 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 receive5-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 phaseⅡandⅢclinical 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
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。
文摘Amplification of the human epidermal growth factor receptor 2(HER2)gene and overexpression of the HER2protein 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 receive5-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 phaseⅡandⅢclinical 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.
