Phase III, Double-Blind, Randomized Study Comparing Lapatinib Plus Paclitaxel With Placebo Plus Paclitaxel As First-Line Treatment for Metastatic Breast Cancer
Phase III, Double-Blind, Randomized Study Comparing Lapatinib Plus Paclitaxel With Placebo Plus Paclitaxel As First-Line Treatment for Metastatic Breast Cancer
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DOI：
10.1200/jco.2008.16.2578
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发表时间：
2008-12-01
影响因子：
45.3
通讯作者：
Press, Michael F.
中科院分区：
文献类型：
--
作者：
Di Leo, Angelo;Gomez, Henry L.;Press, Michael F.
目的：selapatinib是一种表皮生长因子受体（EGFR/ErbB1）和人表皮生长因子受体2 （HER-2/ErbB2）的双酪氨酸激酶抑制剂，对HER-2阳性的局部晚期或转移性乳腺癌（MBC）有效。这项III期试验评估了拉帕替尼在her -2阴性和her -2非特征性MBC中的疗效。患者和方法：女性MBC患者随机分配到一线治疗紫杉醇175 mg/m(2)，每3周加拉帕替尼1500 mg/d或安慰剂。使用荧光原位杂交和免疫组织化学对HER-2状态进行预先计划的回顾性评估。主要终点为进展时间（TTP）；次要终点为客观缓解率（ORR）、临床获益率（CBR）、无事件生存期（EFS）和总生存期（OS）。结果在意向治疗人群（n = 579）中，尽管ORR和CBR存在差异，但治疗组之间的TTP、EFS或OS无显著差异。在86例her -2阳性患者（15%）中，与紫杉醇-安慰剂相比，紫杉醇-拉帕替尼治疗导致TTP、EFS、ORR和CBR的统计学显著改善。在her -2阴性患者中，治疗组之间没有观察到任何终点的差异。最常见的不良反应是脱发、皮疹和腹泻。紫杉醇-拉帕替尼组腹泻和皮疹的发生率明显更高。心脏事件发生率很低，治疗组之间没有观察到差异。结论her -2阴性或her -2未检测的MBC患者在紫杉醇中加入拉帕替尼并没有获益。然而，一线紫杉醇-拉帕替尼治疗可显著改善her -2阳性患者的临床结果。在早期和转移性her -2阳性乳腺癌患者中，该联合治疗的疗效和安全性的前瞻性评估正在进行中。
PurposeLapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER-2/ErbB2), is effective against HER-2-positive locally advanced or metastatic breast cancer (MBC). This phase III trial evaluated the efficacy of lapatinib in HER-2-negative and HER-2-uncharacterized MBC.Patients and MethodsWomen with MBC were randomly assigned to first-line therapy with paclitaxel 175 mg/m(2) every 3 weeks plus lapatinib 1,500 mg/d or placebo. A preplanned retrospective evaluation of HER-2 status was performed using fluorescence in situ hybridization and immunohistochemistry. The primary end point was time to progression (TTP); secondary end points were objective response rate (ORR), clinical benefit rate (CBR), event-free survival (EFS), and overall survival (OS).ResultsIn the intent-to-treat population (n = 579), there were no significant differences in TTP, EFS, or OS between treatment arms, although differences in ORR and CBR were noted. In 86 HER-2-positive patients (15%), treatment with paclitaxel-lapatinib resulted in statistically significant improvements in TTP, EFS, ORR, and CBR compared with paclitaxel-placebo. No differences between treatment groups were observed for any end point in HER-2-negative patients. The most common adverse events were alopecia, rash, and diarrhea. The incidence of diarrhea and rash was significantly higher in the paclitaxel-lapatinib arm. The rate of cardiac events was low, and no difference was observed between treatment arms.ConclusionPatients with HER-2-negative or HER-2-untested MBC did not benefit from the addition of lapatinib to paclitaxel. However, first-line therapy with paclitaxel-lapatinib significantly improved clinical outcomes in HER-2-positive patients. Prospective evaluation of the efficacy and safety of this combination is ongoing in early and metastatic HER-2-positive breast cancer patients.