Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer.
Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer.
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DOI：
10.1186/1471-2407-9-367
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发表时间：
2009-10-17
期刊：
影响因子：
3.8
通讯作者：
Steger GG
中科院分区：
文献类型：
--
作者：
Bartsch R;De Vries C;Pluschnig U;Dubsky P;Bago-Horvath Z;Gampenrieder SP;Rudas M;Mader RM;Rottenfusser A;Wiltschke C;Gnant M;Zielinski CC;Steger GG
在Her 2阳性晚期乳腺癌中，曲妥珠单抗的前期使用已得到充分确立。一线治疗进展后，患者可转换为拉帕替尼治疗。然而，其他人仍然是继续抗体治疗的候选人（治疗超过进展）。在这里，我们的目的是确定预测二线曲妥珠单抗治疗活性的因素。97例接受>一线含曲妥珠单抗治疗的患者可用于本分析。通过免疫组织化学确定Her 2-状态，如果获得2+评分，则通过FISH重新分析。二线治疗的至疾病进展时间（TTP）定义为主要研究终点。使用Kaplan-Meier乘积限法估计TTP和总生存期（OS）。应用多变量分析（考克斯比例风险模型，多项逻辑回归）以确定与TTP、缓解、OS和脑转移发生率相关的因素。p值< 0.05被认为表示统计学显著性。基于曲妥珠单抗的二线治疗的中位TTP为7个月（95% CI 5.74-8.26），基于曲妥珠单抗的一线治疗的中位TTP为8个月（95% CI 6.25-9.74）（n.s.）。在多变量模型中，临床或组织病理学特征均不能可靠预测基于曲妥珠单抗的二线治疗的活性。OS为43个月，表明曲妥珠单抗多线治疗患者的生存期改善。在3例患者中观察到心脏功能显著恶化; 40.2%在二线曲妥珠单抗治疗期间或之后发生脑转移。曲妥珠单抗在进展后显示出相当大的活性。研究的变量均与二线治疗的活性无关。为了预测二线曲妥珠单抗的活性，似乎有必要评价已知赋予曲妥珠单抗耐药性的因素。
In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression). Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy. Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP) on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS) were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression) were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values < 0.05 were considered to indicate statistical significance. Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26), and 8 months (95% CI 6.25-9.74) on first-line, respectively (n.s.). In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter. Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.
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