Trastuzumab Rechallenge After Lapatinib- and Trastuzumab-Resistant Disease Progression in HER2-Positive Breast Cancer
Trastuzumab Rechallenge After Lapatinib- and Trastuzumab-Resistant Disease Progression in HER2-Positive Breast Cancer
复制标题
DOI：
10.1016/j.clbc.2015.06.002
复制
发表时间：
2015-12-01
影响因子：
3.1
通讯作者：
Ito, Yoshinori
中科院分区：
文献类型：
--
作者：
Araki, Kazuhiro;Fukada, Ippei;Ito, Yoshinori
对于拉帕替尼和曲妥珠单抗耐药的her2晚期疾病进展，尚未建立最佳管理。在这项回顾性研究中，我们重点研究了50例曲妥珠单抗和拉帕替尼耐药疾病进展后再次接受曲妥珠单抗治疗的患者。各种化疗联合曲妥珠单抗再挑战具有不同的疗效，无论先前的抗her2治疗是否具有临床益处。曲妥珠单抗再挑战联合各种化疗对一些抗her2治疗耐药的her2阳性疾病有效。背景：多种抗her2疗法改善了her2阳性乳腺癌患者的预后。然而，拉帕替尼（LAP）和曲妥珠单抗（Tmab）耐药疾病进展的最佳管理尚未建立。我们审查了我们机构的数据，以帮助寻找最佳实践。患者和方法：2009年6月至2013年3月，74例her2阳性晚期乳腺癌（ABC）患者接受LAP联合卡培他滨（LAPCAP）治疗。再次接受tmab化疗的患者被确定，重点关注基线特征、化疗和疗效。该研究重点关注50例lapcap耐药疾病进展（LAPCAP-PD）后再次接受Tmab治疗的患者的临床结果，评估肿瘤反应和临床获益（CB）。无进展生存期（PFS）被用作Tmab再挑战疗效的预测替代指标。结果：所有患者均接受Tmab和lap为基础的化疗预处理。在中位随访7.9个月时，PFS为4.6个月，LAPCAP-PD后总生存期为33.7个月。再次接受以tmab为基础的化疗包括23例吉西他滨（GEM）， 14例长春瑞滨，5例紫杉烷，2例内分泌治疗等。CB率为32%，其中1例完全缓解，3例部分缓解，12例病情稳定6个月。尽管接受微管抑制剂（MTIs）治疗的患者的中位PFS比GEM治疗的患者更长，但无论先前的LAPCAP是否有CBs，各种化疗都有不同的疗效。结论：Tmab再挑战联合MTIs和一种时间禁忌药物对部分LAPCAP-PD her2阳性ABC有效。
Optimal management has yet to be established for lapatinib- and trastuzumab-resistant HER2-advanced disease progression. In this retrospective study we focused on 50 patients re-treated with trastuzumab after trastuzumab-and lapatinib-resistant disease progression. Various chemotherapies in combination with trastuzumab rechallenge had different efficacy regardless of whether previous anti-HER2 therapies had clinical benefits. Trastuzumab rechallenge combined with various chemotherapies is effective against some anti-HER2 therapy-resistant HER2-positive disease.Background: Multiple anti-HER2 therapies have improved the outcome for patients with HER2-positive breast cancer. However, optimal management has yet to be established for lapatinib (LAP)- and trastuzumab (Tmab)-resistant disease progression. Data from our institution were reviewed to contribute to the search for best practices. Patients and Methods: Between June 2009 and March 2013, 74 HER2-positive advanced breast cancer (ABC) patients were treated with LAP with capecitabine (LAPCAP). Patients re-treated with Tmab-based chemotherapies were identified, with a focus on baseline characteristics, chemotherapies, and efficacy. The study focused on the clinical outcomes of 50 patients re-treated with Tmab after LAPCAP-resistant disease progression (LAPCAP-PD), with an assessment of tumor response and clinical benefit (CB). Progression-free survival (PFS) was used as a predictive surrogate marker for the efficacy of Tmab rechallenge. Results: All patients were pretreated with Tmab- and LAP-based chemotherapies. At a median follow-up of 7.9 months, PFS was 4.6 months, and overall survival was 33.7 months after LAPCAP-PD. Rechallenges with Tmab-based chemotherapies included gemcitabine (GEM) in 23 patients, vinorelbine in 14, taxanes in 5, endocrine treatments in 2, and others. The CB rate was 32%, including complete response for 1, partial response for 3, and > 6 months of stable disease for 12. Although the median PFS was longer for patients treated with microtubule inhibitors (MTIs) than with GEM, various chemotherapies had different efficacy regardless of whether or not previous LAPCAP had CBs. Conclusion: Tmab rechallenge combined with not only MTIs but also an antime-tabolite agent is effective against some LAPCAP-PD HER2-positive ABC.