Cixutumumab for patients with recurrent or refractory advanced thymic epithelial tumours: a multicentre, open-label, phase 2 trial

被引：97

作者：

Rajan, Arun ^{[1
]}

Carter, Corey A. ^{[1
]}

Berman, Arlene ^{[1
]}

Cao, Liang ^{[2
]}

Kelly, Ronan J. ^{[1
]}

Thomas, Anish ^{[1
]}

Khozin, Sean ^{[1
]}

Chavez, Ariel Lopez ^{[1
]}

Bergagnini, Isabella ^{[3
]}

Scepura, Barbara ^{[1
]}

Szabo, Eva ^{[1
]}

Lee, Min-Jung ^{[1
]}

Trepel, Jane B. ^{[1
]}

Browne, Sarah K. ^{[4
]}

Rosen, Lindsey B. ^{[4
]}

Yu, Yunkai ^{[2
]}

Steinberg, Seth M. ^{[5
]}

Chen, Helen X. ^{[1
]}

Riely, Gregory J. ^{[3
]}

Giaccone, Giuseppe ^{[1
]}

机构：

[1] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[2] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA

[3] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[4] NIAID, NIH, Bethesda, MD 20892 USA

[5] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA

来源：

LANCET ONCOLOGY | 2014年 / 15卷 / 02期

基金：

美国国家卫生研究院;

关键词：

FACTOR-I RECEPTOR; ADVANCED THYMOMA; ONCOLOGY-GROUP; SOLID TUMORS; INSULIN; ANTIBODY; AUTOIMMUNITY; GEMCITABINE; EXPRESSION; INHIBITOR;

D O I：

10.1016/S1470-2045(13)70596-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background No standard treatment exists for refractory or relapsed advanced thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody targeting the insulin-like growth factor 1 receptor in thymic epithelial tumours after failure of previous chemotherapy. Methods Between Aug 25, 2009, and March 27, 2012, we did a multicentre, open-label, phase 2 trial in patients aged 18 years or older with histologically confirmed recurrent or refractory thymic epithelial tumours. We enrolled individuals who had progressed after at least one previous regimen of platinum-containing chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had measurable disease and adequate organ function. Eligible patients received intravenous cixutumumab (20 mg/kg) every 3 weeks until disease progression or development of intolerable toxic effects. The primary endpoint was the frequency of response, analysed on an intention-to-treat basis. We also did pharmacodynamic studies. This trial is registered with ClinicalTrials.gov, number NCT00965250. Findings 49 patients were enrolled (37 with thymomas and 12 with thymic carcinomas) who received a median of eight cycles of cixutumumab (range 1-46). At the final actuarial analysis when follow-up data were updated (Nov 30, 2012), median potential follow-up (from on-study date to most current follow-up date) was 24.0 months (IQR 17.3-36.9). In the thymoma cohort, five (14%) of 37 patients (95% CI 5-29) achieved a partial response, 28 had stable disease, and four had progressive disease. In the thymic carcinoma cohort, none of 12 patients (95% CI 0-26) had a partial response, five had stable disease, and seven had progressive disease. The most common grade 3-4 adverse events in both cohorts combined were hyperglycaemia (five [10%]), lipase elevation (three [6%]), and weight loss, tumour pain, and hyperuricaemia (two each [4%]). Nine (24%) of 37 patients with thymoma developed autoimmune conditions during treatment (five were new-onset disorders), the most common of which was pure red-cell aplasia. Two (4%) patients died; one was attributed to disease progression and the other to disease-related complications (respiratory failure, myositis, and an acute coronary event), which could have been precipitated by treatment with cixutumumab. Interpretation Cixutumumab monotherapy is well-tolerated and active in relapsed thymoma. Development of autoimmunity during treatment needs further investigation.

引用

页码：191 / 200

页数：10