一项关于拉帕替尼联合卡培他滨、长春瑞滨或吉西他滨用于紫杉烷类治疗后进展的HER2阳性转移性乳腺癌患者的II期随机研究（拉丁美洲肿瘤协作组0801研究）
A Phase II Randomized Study of Lapatinib Combined With Capecitabine, Vinorelbine, or Gemcitabine in Patients With HER2-Positive Metastatic Breast Cancer With Progression After a Taxane (Latin American Cooperative Oncology Group 0801 Study).
作者信息
Gómez Henry L, Neciosup Silvia, Tosello Célia, Mano Max, Bines José, Ismael Gustavo, Santi Patrícia X, Pinczowski Hélio, Nerón Yeni, Fanelli Marcello, Fein Luis, Sampaio Carlos, Lerzo Guillermo, Capó Adolfo, Zarba Juan J, Blajman César, Varela Mirta S, Martínez-Mesa Jeovany, Werutsky Gustavo, Barrios Carlos H
机构信息
Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
Instituto Brasileiro de Controle do Câncer, São Paulo, São Paulo, Brazil.
出版信息
Clin Breast Cancer. 2016 Feb;16(1):38-44. doi: 10.1016/j.clbc.2015.10.005. Epub 2015 Nov 10.
BACKGROUND
Novel targeted agents and combinations have become available in multiple lines of treatment for human epidermal growth factor receptor 2-positive (HER2(+)) metastatic breast cancer (MBC). In this context, alternatives to the lapatinib (L) and capecitabine (C) regimen, evaluating L combined with other cytotoxic drugs, are warranted.
PATIENTS AND METHODS
In the present phase II, multicenter study, patients with HER2(+) MBC with progression after taxane were randomized between L, 1250 mg, combined with C, 2000 mg/m(2) on days 1 to 14 (LC), vinorelbine (V), 25 mg/m(2) on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m(2) on days 1 and 8 (LG), every 21 days. The primary endpoint was the overall response rate.
RESULTS
A total of 142 patients were included from 2009 to 2012. No differences were found in the patient baseline characteristics. The median age was 51 years, 69% were postmenopausal, 32% had liver metastasis, 57% were hormone receptor negative, and 48% had been previously treated with trastuzumab. The overall response rate was 49% (95% confidence interval [CI], 34.8%-63.4%), 56% (95% CI, 40%-70.4%), and 41% (95% CI, 27%-56.8%) in the LC, LV, and LG groups, respectively. The median progression-free survival was 9 months in the LC arm and 7 months in the other 2 arms (P = .28). The most common grade 3 and 4 adverse events were hand-foot syndrome (18%), diarrhea (6%), and increased alanine aminotransferase/aspartate aminotransferase (4%) in the LC arm; neutropenia (36%), diarrhea (9%), and febrile neutropenia (6%) in the LV arm; and neutropenia (47%), alanine aminotransferase/aspartate aminotransferase (13%), and rash (4%) in the LG arm.
CONCLUSION
LV and LG seem to be active combinations in patients with HER2(+) MBC after taxane failure. The overall toxicity was manageable in all regimens.
背景
新型靶向药物及联合用药已应用于人类表皮生长因子受体2阳性（HER2(+)）转移性乳腺癌（MBC）的多线治疗。在此背景下，有必要评估拉帕替尼（L）联合其他细胞毒性药物，作为拉帕替尼（L）与卡培他滨（C）方案的替代方案。
患者与方法
在这项II期多中心研究中，紫杉烷治疗后病情进展的HER2(+) MBC患者被随机分为三组，分别接受L（1250 mg）联合C（2000 mg/m²，第1至14天）（LC组）、长春瑞滨（V）（25 mg/m²，第1天和第8天）（LV组）或吉西他滨（G）（1000 mg/m²，第1天和第8天）（LG组）治疗，每21天为一个周期。主要终点为总缓解率。
结果
2009年至2012年共纳入142例患者。患者基线特征无差异。中位年龄为51岁，69%为绝经后女性，32%有肝转移，57%激素受体阴性，48%曾接受曲妥珠单抗治疗。LC组、LV组和LG组的总缓解率分别为49%（95%置信区间[CI]，34.8%-63.4%）、56%（95%CI，40%-70.4%）和41%（95%CI，27%-56.8%）。LC组的中位无进展生存期为9个月，其他两组为7个月（P = 0.28）。LC组最常见的3级和4级不良事件为手足综合征（18%）、腹泻（6%）和丙氨酸氨基转移酶/天冬氨酸氨基转移酶升高（4%）；LV组为中性粒细胞减少（36%）、腹泻（9%）和发热性中性粒细胞减少（6%）；LG组为中性粒细胞减少（47%）、丙氨酸氨基转移酶/天冬氨酸氨基转移酶（13%）和皮疹（4%）。
结论
紫杉烷治疗失败的HER2(+) MBC患者中，LV和LG似乎是有效的联合方案。所有方案的总体毒性均可控制。
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