跨线曲妥珠单抗联合不同化疗方案治疗HER2阳性晚期乳腺癌的临床研究

Clinical Observation of Trastuzumab Across Multiple Lines plus Different Chemotherapy Regimens on HER2 Positive Advanced Breast Cancer Patients

目的观察跨线曲妥珠单抗联合不同化疗方案治疗人表皮生因子受体2(human epidermal growth factor receptor 2,HER2)阳性晚期乳腺癌的疗效、不良反应和生存期。方法收集2009年1月至2014年6月间应用跨线曲妥珠单抗(H)联合不同化疗方案治疗HER2阳性的晚期乳腺癌患者71例,均完成一线H治疗,30例患者疾病进展后继续二线H治疗,19例患者疾病再次进展后继续三线H治疗,主要观察疗效、不良反应、生存情况及预后分析。结果一、二、三线治疗中,曲妥珠单抗联合紫杉类方案和联合非紫杉类方案相比在有效率(RR)和临床获益率(clinical benefi t rate,CBR)方面差异均无统计学意义(P>0.05)。一、二、三线治疗的中位无进展生存时间(PFS)和中位总生存时间(OS)分别为14、9、4月和26、39、53月,总的中位PFS为11月,总的中位OS为36月。一线治疗的PFS较二、三线治疗明显延长(P=0.000),曲妥珠单抗持续应用至三线的中位OS较仅一线治疗的有延长(P=0.008)。全组患者的1、2、3年生存率分别为88%、66%、39%。71例患者中14例出现了17次心脏相关事件,1例患者因左心室射血分数(LVEF)下降至48%停止曲妥珠单抗治疗,无治疗相关性死亡发生。在OS的Log rank单因素分析中,术后淋巴结转移的个数、有无脑转移、治疗线数、一线治疗的PFS时间与OS有关(P=0.026,P=0.042,P=0.028,P=0.005)。在OS的多因素Cox比例风险模型分析中,治疗线数、有无脑转移、DFS和一线PFS时间为对OS有影响的独立因素(P=0.004,P=0.021,P=0.018,P=0.000)。结论在HER-2阳性晚期乳腺癌治疗中,疾病进展后跨线曲妥珠单抗联合化疗的疗效优于未继续使用曲妥珠单抗的方案,曲妥珠单抗的跨线使用可以使患者持续获益,跨线曲妥珠单抗联合化疗的方案疗效确切,不良反应可以耐受,值得进一步研究。

Objective To investigate the effi cacy,adverse effect and survival of continued use of trastuzumab across multiple lines plus different chemotherapy regimens on HER2 positive advanced breast cancer patients.Methods Seventy-one patients with HER2 positive advanced breast cancer were treated with trastuzumab across multiple lines plus different chemotherapy regimens from Jan.,2009 to June,2014.All 71 patients received trastuzumab as a first-line therapy.After disease progression,trastuzumab was administered as a second-line therapy on 30 patients,19 patients were treated with trastuzumab as a third-line therapy beyond disease progression again.We evaluated the clinical effi cacy,side effect and outcome.Results In the first-,second-,third-line treatment,there was no statistical difference in response rate（RR） or clinical benefi t rate（CBR） between trastuzumab combined with taxane drugs and non-taxane drugs（P〉0.05）.The median progression free survival（PFS） and overall survival（OS） were 14,9,4 months and 26,39,53 months in the first-,second-,third-line treatment.The total PFS was 11 months and the total OS was 36 months.The PFS in the first-line therapy was longer than those in the second-and third-line therapies（P=0.000）.The OS of continued use of trastuzumab to the third-line therapy was longer than that only to the firstline therapy（P=0.008）.The 1-,2-and 3-year survival rates were 88%,66% and 39%.Fourteen of the 71 patients had 17 cardiac events;one patient was terminated trastuzumab therapy because of a left ventricular ejection fraction（LVEF） decreasing to 48%,but no fatal cardiac event was reported.The number of lymphatic metastasis,brain metastases,different treatment lines and the PFS of the fi rst-line treatment were concerned with OS in Log rank single factor analysis（P=0.026,P=0.042,P=0.028,P=0.005）.The different treatment lines,brain metastases,DFS and the PFS of the fi rst-line treatment were independently prognostic factors for OS in Cox proportional hazards model analysis（P=0.004,P=0.021,P=0.018,P=0.000）.Conclusion For patients with HER2-positive advanced breast cancer,trastuzumab across multiple lines combined with different chemotherapy is superior to those without continued trastuzumab treatment.Patients are benefit continually from trastuzumab treatment beyond disease progression.The administration of trastuzumab across multiple lines combined with chemotherapy is effective,well tolerated and worthy of further study.