凡德他尼治疗RET重排的非小细胞肺癌患者有效

Vandetanib in patients with previously treated RET-rearranged advanced non-small-cell lung cancer (LURET): an open-label, multicentre phase 2 trial. 凡德他尼治疗既往治疗过的RET重排的晚期非小细胞肺癌患者（LURET）：一项标签开放、多中心2期试验。山东省肿瘤医院呼吸肿瘤内科张品良

Abstract 摘要

BACKGROUND: 背景：

RET rearrangements are rare oncogenic alterations in non-small-cell lung cancer (NSCLC). Vandetanib is a multitargeted tyrosine kinase inhibitor exhibiting RET kinase activity. We aimed to assess the efficacy and safety of vandetanib in patients with advanced RET-rearranged NSCLC. 在非小细胞肺癌（NSCLC）中RET重排是罕见的致癌突变。凡德他尼是一个对RET激酶具有活性的多靶点酪氨酸激酶抑制剂。我们的目的是评估凡德他尼治疗晚期RET重排的非小细胞肺癌患者的疗效和安全性。

METHODS: 方法：

In this open-label, multicentre, phase 2 trial (LURET), patients with advanced RET-rearranged NSCLC continuously received 300 mg of oral vandetanib daily. RET-positive patients were screened using a nationwide genomic screening network of about 200 participating institutions. Primary endpoint was the independently assessed objective response in eligible patients. This study is registered with UMIN-CTR, number UMIN000010095.
在这项标签开放、多中心2期试验（LURET）中，晚期RET重排的非小细胞肺癌患者连续口服凡德他尼300 mg每天一次。使用大约200个参与机构的一个全国性的基因筛查网络筛选RET阳性患者。主要终点是在符合条件的患者中独立评估的客观疗效。本研究已在UMIN-CTR注册，编号UMIN000010095。

FINDINGS:
发现：

Between Feb 7, 2013, and March 19, 2015, 1536 patients with EGFR mutation-negative NSCLC were screened, of whom 34 were RET-positive (2%) and 19 were enrolled. Among 17 eligible patients included in primary analysis, nine (53% [95% CI 28-77]) achieved an objective response, which met the primary endpoint. In the intention-to-treat population of all 19 patients treated with vandetanib, nine (47% [95% CI 24-71]) achieved an objective response. At the data cutoff, median progression-free survival was 4·7 months (95% CI 2·8-8·5). The most common grade 3 or 4 adverse events were hypertension (11 [58%]), diarrhoea (two [11%]), rash (three [16%]), dry skin (one [5%]), and QT prolongation (two [11%]).
在2013年2月7日至2015年3月19日间，筛选了1536例EGFR突变阴性的非小细胞肺癌患者，其中34例RET阳性（2%）入组19例。在初步分析中包括的符合条件的17例患者中，9例（53% [95% CI 28-77]）取得客观疗效，从而达到了主要终点。在所有凡德他尼治疗的19例患者的意向性治疗人群中，9例（47%[ 95% CI 24-71 ]）取得客观疗效。在数据截止时，中位无进展生存期为4.7个月（95% CI 2.8-8.5）。最常见的3或4级不良事件为高血压（11 [58%]）、腹泻（2 [11%]）、皮疹（3 [16%]）、皮肤干燥（1 [5%]）和QT间期延长（2 [11%]）。

INTERPRETATION:
解读：

Vandetanib showed clinical antitumour activity and a manageable safety profile in patients with advanced RET-rearranged NSCLC. Our results define RET rearrangement as a new molecular subgroup of NSCLC suitable for targeted therapy.
在晚期RET重排的非小细胞肺癌患者中，凡德他尼显示出临床抗肿瘤活性和易控制的安全性。我们的研究结果明确了RET重排是一种新的适于靶向治疗的非小细胞肺癌分子亚型。