Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non-adenoid cystic carcinoma malignant tumors of the salivary glands
Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non-adenoid cystic carcinoma malignant tumors of the salivary glands
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DOI：
10.1200/jco.2007.11.8612
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发表时间：
2007-09-01
影响因子：
45.3
通讯作者：
Siu, Lillian L.
中科院分区：
文献类型：
--
作者：
Agulnik, Mark;Cohen, Ezra W. E.;Siu, Lillian L.
ERBB2和/或表皮生长因子受体（EGFR）的目的表达与恶性唾液腺肿瘤（MSGTS）的生物学攻击性和预后不良有关。进行了这项II期研究，以确定Lapatinib的抗肿瘤活性，Lapatinib是EGFR和ERBB2酪氨酸激酶活性的双重抑制剂，在MSGTS.patiats和方法室内具有进行性，复发性或转移性腺苷腺苷癌（ACC）免疫组织化学表达1 + 1 + 1 +表达1 +的方法的方法。 EGFR和/或2 + ERBB2用lapatinib处理每天1,500毫克，在两个阶段队列中。非ACC MSGT的患者被视为单独的单阶段队列。筛查的62例患者，33例（88％）ACC中的29例，29例（97％）非ACC患者中有28例表达EGFR和/或ERBB2。该研究已纳入40例进行性疾病的患者。在19例可评估的ACC患者中，没有客观反应，15例患者（79％）患有稳定疾病（SD），9例患者（47％）患有SD> = 6个月，4例患者（21％）患有进行性疾病（PD） ）。对于17名可评估的非ACC患者，没有客观反应，八名患者（47％）患有SD，四名患者（24％）患有SD> = 6个月，而9例患者（53％）患有PD。最常见的不良事件是1至2级腹泻，疲劳和皮疹。采购了八个配对的肿瘤活检以进行相关研究；结果与临床结局无关。确定的尚未观察到反应，lapatinib的耐受性良好，延长肿瘤稳定> = 6个月，在36％（95％CI，21％至54％）的可评估患者中。 Lapatinib在MGST中的抗肿瘤作用主要是细胞抑制作用，因此可以考虑对其他分子靶向剂的评估，或者可以考虑与Lapatinib的组合。应该继续努力以更好地了解这种异质性恶性肿瘤的生物学。
PurposeExpression of erbB2 and/or epidermal growth factor receptor (EGFR) is associated with biologic aggressiveness and poor prognosis in malignant salivary gland tumors (MSGTs). This phase II study was conducted to determine the antitumor activity of lapatinib, a dual inhibitor of EGFR and erbB2 tyrosine kinase activity, in MSGTs.Patients and MethodsPatients with progressive, recurrent, or metastatic adenoid cystic carcinoma (ACC) immunohistochemically expressing at least 1 + EGFR and/or 2 + erbB2 were treated with lapatinib 1,500 mg daily, in a two-stage cohort. Patients with non-ACC MSGTs were treated as a separate single-stage cohort.ResultsOf 62 patients screened, 29 of 33 (88%) ACC and 28 of 29 (97%) non-ACC patients expressed EGFR and/or erbB2. Forty patients with progressive disease were enrolled onto the study. Among 19 assessable ACC patients, there were no objective responses, 15 patients (79%) had stable disease (SD), nine patients (47%) had SD >= 6 months, and four patients (21%) had progressive disease (PD). For 17 assessable non-ACC patients, there were no objective responses, eight patients (47%) had SD, four patients (24%) had SD >= 6 months, and nine patients (53%) had PD. The most frequent adverse events were grade 1 to 2 diarrhea, fatigue, and rash. Eight paired tumor biopsies for correlative studies were procured; results did not correlate with clinical outcome.ConclusionAlthough no responses were observed, lapatinib was well tolerated, with prolonged tumor stabilization of >= 6 months in 36% (95% CI, 21% to 54%) of assessable patients. The antitumor effects of lapatinib in MGSTs appear mainly cytostatic, hence evaluation of other molecular targeted agents, or combinations with lapatinib, may be considered. Continued efforts should be made to gain better understanding into the biology of this heterogeneous group of malignancies.