Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial
Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial
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DOI：
10.1093/annonc/mdw559
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发表时间：
2017-02-01
影响因子：
50.5
通讯作者：
Park, K.
中科院分区：
文献类型：
--
作者：
Lee, S. -H.;Lee, J. -K.;Park, K.
背景资料：涉及RET的染色体重排，在约1%的非小细胞肺癌（NSCLC）中发现，定义了一个独特的分子子集。我们进行了这项研究，以检查凡德他尼300毫克，每天在这个patient population.Patients和方法的有效性和安全性：这项研究是一项多中心，开放标签，II期临床试验。如果患者患有转移性或复发性NSCLC伴RET重排（经荧光原位杂交证实）、对含铂二联化疗有进展性疾病且体能状态为0-2，则入组研究。主要终点为客观缓解率。结果：2013年7月至2015年10月，共有18例患者入选本研究。患者年龄为35-71岁; 3例体能状态为2，大多数为重度预治疗人群（72%的患者既往接受过两种不同的化疗方案）。在17名可评估的患者中，3名患者部分缓解（客观缓解率>= 18%），8名患者病情稳定（疾病控制率= 65%）。在这些患者中，8例患者的部分缓解或疾病稳定持续超过6个月。Vandetanib还显示无进展生存期为4.5个月，中位随访时间为14个月，总生存期为11.6个月。安全性特征与先前的凡德他尼研究相当。大多数凡德他尼相关的不良事件是轻度的，主要是高血压和皮疹（>70%的患者）。3级毒性包括高血压（n = 3）、QT间期延长（2）和转氨酶升高（1），因此4例患者的剂量降低。没有与4级或5级毒性相关的不良事件。结论：凡德他尼在预治疗的晚期NSCLC携带RET重排患者中具有中度活性。
Background: Chromosomal rearrangements involving RET, which are found in about 1% of non-small cell lung cancer (NSCLC), define a unique molecular subset. We performed this study to examine the efficacy and safety of vandetanib 300 mg daily in this patient population.Patients and methods: This study was a multi-center, open-label, phase II clinical trial. Patients were enrolled if they had metastatic or recurrent NSCLC with a RET rearrangement, which was confirmed by fluorescence in situ hybridization, had progressive disease against platinum-based doublet chemotherapy, and had a performance status of 0-2. The primary endpoint was the objective response rate.Results: A total of 18 patients were enrolled in this study between July 2013 and October 2015. Patients were aged 35-71 years; three had a performance status of 2, and the majority were a heavily pretreated population (two different previous chemotherapy regimens in 72% of the patients). Among the 17 evaluable patients, three had a partial response (objective response rate >= 18%) and eight had a stable disease (disease control rate = 65%). Among these patients, the partial response or disease stabilization was durable for more than 6 months in eight patients. Vandetanib also showed a progression-free survival of 4.5 months, and an overall survival of 11.6 months during a median follow-up duration of 14 months. The safety profile was comparable with previous studies of vandetanib. Most vandetanib-related adverse events were mild with prevalent hypertension and rash (in>70% of patients). Grade 3 toxicity included hypertension (n = 3), QT prolongation (2), and elevation of aminotransferases (1), and as a consequence the dose was reduced in four patients. There were no adverse events associated with grade 4 or 5 toxicity.Conclusion: Vandetanib is moderately active in pretreated patients with advanced NSCLC-harboring RET rearrangements.