HER2阳性转移性乳腺癌多线靶向治疗耐药后再次使用曲妥珠单抗疗效及预后分析  

Efficacy and prognostic analysis of retreatment with trastuzumab-based therapy after multi-fine targeted therapy resistance in HER2-positive metastatic breast cancer

作　　者：边莉[1] 江泽飞[1] 王涛[1] 宋金洁[1] 郭芸菲[1] 张会强[1] 张少华[1] 吴世凯[1] 宋三泰[1] 

机构地区：[1]军事医学科学院附属医院乳腺肿瘤科,北京100071

出　　处：《中华医学杂志》2013年第1期48-52,共5页National Medical Journal of China

摘　　要：目的探讨HER2阳性转移性乳腺癌患者在多线靶向治疗相继耐药后，再度使用曲妥珠单抗疗效和预后的预测因素。方法入选2008年7月至2010年7月在军事医学科学院附属医院乳腺肿瘤科治疗的HER2阳性转移性乳腺癌患者29例，均先后接受曲妥珠单抗、拉帕替尼以及再次曲妥珠单抗治疗。其中21例首次曲妥珠单抗治疗出现疾病进展，所有患者均应用拉帕替尼治疗至疾病进展，之后均再次应用曲妥珠单抗治疗至疾病进展或死亡。采用Log—rank检验进行单因素分析，采用Cox比例风险回归模型进行多因素分析。结果首次曲妥珠单抗治疗进展患者与未进展患者再次使用曲妥珠单抗治疗疗效差异无统计学意义。单因素分析表明“既往拉帕替尼治疗TTP时间”是再次曲妥珠单抗治疗中位无进展生存期（PFS）的影响因素（P〈0．0001），“停用拉帕替尼至再次使用曲妥珠单抗治疗间隔时间”是中位总生存期（OS）的影响因素（P=0．008）。多因素分析显示既往拉帕替尼治疗1TrP时间〉12周患者与≤12周患者相比（HR=0．02，P=0．003）、前后两次曲妥珠单抗治疗间隔时间≤1年的患者与〉1年的患者相比（HR=0．26，P=0．03）中位PFS显著延长；停用拉帕替尼至再次使用曲妥珠单抗治疗间隔时间≤4周患者与〉4周的患者相比死亡风险降低了89％（HR=0．11，P=0．004）。结论既往拉帕替尼治疗TTP时间、两次曲妥珠单抗治疗间隔时间是再次曲妥珠单抗治疗PFS的预测因素。停用拉帕替尼至曲妥珠单抗治疗间隔时间是再次使用曲妥珠单抗患者重要的独立预后因素，提示HER2阳性转移性乳腺癌患者应持续应用抗HER2靶向治疗。Objective To evaluate the predictive factors for efficacy and prognosis of retreatment trastuzumab in the patients with HER2 positive metastatic breast cancer （MBC） developing successive resistance to rnuhi-line targeting therapies. Methods The data of 29 patients with HER2 positive MBC were collected from July 2008 to July 2010 at our department. All patients were treated with trastuzumab, lapatinib and retreated with trastuzumab sequentially. Twenty-one patients progressed during the initial trastuzumab therapy. All patients were treated with lapatinib to disease progression and retreated with trastuzumab to disease progression or death subsequently. A Log-rank test was used for univariate analysis and a Cox regression model was employed for multivariate analysis. Results The efficacy showed no significant difference between the patients with progression or those without progression during the initial trastuzumab therapy. The time-to-progression （T＇FP） of prior lapatinib therapy was an influencing factor of median progression-free survival （PFS） （P 〈 0. 0001 ） and the duration from discontinuation of lapatinib to trastuzumab retreatment an influencing factor of median overall survival （OS） （P = 0. 008 ） of trastuzumab retreatment in our univariate analysis. The median PFS of trastuzumab retreatment for patients with TTP of lapatinib therapy 〉 12 weeks （ hazard ratio （HR） = 0. 02, P = 0. 003 ） or whose duration of doubletrastuzumab treatment ≤ 1 year（HR = 0.26, P = 0.03 ） was significantly prolonged in multivariate analysis. Meanwhile, the death risk of patients whose duration from discontinuation of lapatinib to trastuzumab retreatment ≤4 weeks decreased 89 % as compared with trastuzumab retreatment （ HR = 0. 11, P = 0. 004）. Conclusion TFP of prior lapatinib therapy and the duration of double trastuzumab treatment are two predictive factors of PFS of trastuzumab retreatment. And the duration from discontinuation of lapatinib to trastuzumab retreatment is an imp

关 键 词：乳腺肿瘤 肿瘤转移 药物疗法 受体 表皮生长因子 治疗结果 预后 

分 类 号：R737.9[医药卫生—肿瘤]