Clinical Activity of Alectinib in Advanced RET-Rearranged Non-Small Cell Lung Cancer

被引：73

作者：

Lin, Jessica J. ^{[1
]}

Kennedy, Elizabeth ^{[1
]}

Sequist, Lecia V. ^{[1
]}

Brastianos, Priscilla K. ^{[1
]}

Goodwin, Kelly E. ^{[1
]}

Stevens, Sara ^{[1
]}

Wanat, Alexandra C. ^{[1
]}

Stober, Lisa L. ^{[1
]}

Digumarthy, Subba R. ^{[2
]}

Engelman, Jeffrey A. ^{[1
]}

Shaw, Alice T. ^{[1
]}

Gainor, Justin F. ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA

[2] Massachusetts Gen Hosp, Dept Thorac Imaging & Intervent, Boston, MA 02114 USA

来源：

JOURNAL OF THORACIC ONCOLOGY | 2016年 / 11卷 / 11期

关键词：

Alectinib; RET; Tyrosine kinase inhibitor; Lung cancer; NSCLC; CRIZOTINIB; ADENOCARCINOMA; PATIENT; FUSIONS; GENE;

D O I：

10.1016/j.jtho.2016.08.126

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Chromosomal rearrangements involving rearranged during transfection gene (RET) occur in 1% to 2% of NSCLCs and may confer sensitivity to rearranged during transfection (RET) inhibitors. Alectinib is an anaplastic lymphoma kinase tyrosine kinase inhibitor (TKI) that also has anti-RET activity in vitro. The clinical activity of alectinib in patients with RET-rearranged NSCLC has not yet been reported. Methods: We have described four patients with advanced RET-rearranged NSCLC who were treated with alectinib (600 mg twice daily [n = 3] or 900 mg twice daily [n = 1]) as part of single-patient compassionate use protocols or off label use of the commercially available drug. Results: Four patients with metastatic RET-rearranged NSCLC were identified. Three of the four had received prior RET TKIs, including cabozantinib and experimental RET inhibitors. In total, we observed two (50%) objective radiographic responses after treatment with alectinib (one confirmed and one unconfirmed), with durations of therapy of 6 months and more than 5 months (treatment ongoing), respectively. Notably, one of these two patients had his dose of alectinib escalated to 900 mg twice daily and had clinical improvement in central nervous system metastases. In addition, one patient (25%) experienced a best response of stable disease lasting approximately 6 weeks (the drug discontinued for toxicity). A fourth patient who was RET TKI-naive had primary progression while receiving alectinib. Conclusions: Alectinib demonstrated preliminary antitumor activity in patients with advanced RET-rearranged NSCLC, most of whom had received prior RET inhibitors. Larger prospective studies with longer follow-up are needed to assess the efficacy of alectinib in RET-rearranged NSCLC and other RET-driven malignancies. In parallel, development of more selective, potent RET TKIs is warranted. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

引用

页码：2027 / 2032

页数：6

共 16 条

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