拉帕替尼在疾病进展后给药并联合长春瑞滨治疗HER-2/neu阳性晚期乳腺癌的疗效和安全性的II期研究：CECOG LaVie试验结果
Phase II study on the efficacy and safety of Lapatinib administered beyond disease progression and combined with vinorelbine in HER-2/neu- positive advanced breast cancer: results of the CECOG LaVie trial.
作者信息
Thallinger Christiane, Lang Istvan, Kuhar Cvetka Grasic, Bartsch Rupert, Singer Christian F, Petruzelka Lubos, Melichar Bohuslav, Knittelfelder Regina, Brodowicz Thomas, Zielinski Christoph
机构信息
Department of Medicine I and Comprehensive Cancer Center, Clinical Division of Oncology, Medical University Vienna - General Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Central European Cooperative Oncology Group (CECOG), Schlagergasse 6/6, 1090, Vienna, Austria.
出版信息
BMC Cancer. 2016 Feb 18;16:121. doi: 10.1186/s12885-016-2171-y.
BACKGROUND
Vinorelbine constitutes effective chemotherapy for metastatic breast cancer (MBC) and acts synergistically with trastuzumab in HER-2/neu positive disease. The present study was set out to evaluate the efficacy and safety of vinorelbine when combined with lapatinib, an anti-HER2 tyrosine-kinase inhibitor, as late-line regimen administered beyond previous disease progression on prior lapatinib in patients with HER-2/neu- positive MBC.
METHODS
The CECOG LaVie study was designed as open-labeled, single-arm, multicenter phase II trial. Patients had to be pretreated with lapatinib plus chemotherapy, and received lapatinib at a daily dose of 1250 mg in combination with vinorelbine 20 mg/m(2) i.v. on days 1 and 8 of a three-week cycle until disease progression, intolerable toxicity or withdrawal of consent. Progression-free survival (PFS) was defined as primary study endpoint; secondary endpoints included overall survival (OS), response rate according to RECIST 1.1, and safety. The study was terminated early due to poor accrual.
RESULTS
A total number of nine patients were included; lapatinib administered beyond disease progression combined with vinorelbine resulted in a median PFS of 7.7 months (95% CI 0.56-14.91) and a median OS of 23.4 months (95% CI 16.61-30.13), respectively. Partial remission was seen in one of nine patients, three patients had stable disease of > six months, whereas the remaining five patients had primary disease progression. In two patients, modification of vinorelbine dose due to toxicity became necessary; no dose modification was needed for lapatinib. The majority of reported adverse events (AE) were grade 1 and 2 in severity with diarrhea being the most commonly observed AE CONCLUSION: In this heavily pretreated patient population, combination of vinorelbine plus lapatinib showed encouraging activity and was characterized by an acceptable safety profile. Despite the low patient number, lapatinib plus vinorelbine may constitute a potential treatment option in heavily pretreated patients with HER-2/neu-positive MBC previously exposed to lapatinib.
TRIAL REGISTRATION
EudraCT number 2009-016826-15, (15. 10.2009).
背景
长春瑞滨是转移性乳腺癌（MBC）的有效化疗药物，在HER-2/neu阳性疾病中与曲妥珠单抗具有协同作用。本研究旨在评估长春瑞滨与抗HER2酪氨酸激酶抑制剂拉帕替尼联合使用作为晚期治疗方案的疗效和安全性，该方案用于HER-2/neu阳性MBC患者，在先前使用拉帕替尼治疗疾病进展后使用。
方法
CECOG LaVie研究设计为开放标签、单臂、多中心II期试验。患者必须接受过拉帕替尼联合化疗的预处理，并在为期三周的周期的第1天和第8天接受每日剂量1250 mg的拉帕替尼联合20 mg/m²静脉注射长春瑞滨，直至疾病进展、出现无法耐受的毒性或患者撤回同意。无进展生存期（PFS）被定义为主要研究终点；次要终点包括总生存期（OS）、根据RECIST 1.1标准的缓解率和安全性。由于入组情况不佳，该研究提前终止。
结果
共纳入9例患者；在疾病进展后使用拉帕替尼联合长春瑞滨治疗，中位PFS为7.7个月（95%CI 0.56 - 14.91），中位OS为23.4个月（95%CI 16.61 - 30.13）。9例患者中有1例部分缓解，3例患者疾病稳定超过6个月，其余5例患者疾病进展。2例患者因毒性需要调整长春瑞滨剂量；拉帕替尼无需调整剂量。报告的大多数不良事件（AE）严重程度为1级和2级，腹泻是最常见的AE。结论：在这个经过大量预处理的患者群体中，长春瑞滨加拉帕替尼联合治疗显示出令人鼓舞的活性，且安全性可接受。尽管患者数量较少，但拉帕替尼加长春瑞滨可能是先前接受过拉帕替尼治疗的HER-2/neu阳性MBC的大量预处理患者的一种潜在治疗选择。
试验注册
EudraCT编号2009 - 016826 - 15，（2009年10月15日）。
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