SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway-Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy)
SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway-Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy)
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DOI：
10.1016/j.jtho.2019.05.041
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发表时间：
2019-10-01
影响因子：
20.4
通讯作者：
Gandara, David R.
中科院分区：
文献类型：
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作者：
Aggarwal, Charu;Redman, Mary W.;Gandara, David R.
背景：S1400D是Lung-MAP的一项生物标志物驱动的治疗性亚研究，评估成纤维细胞生长因子（FGF）受体（FGFR）抑制剂AZD4547在FGF通路激活的鳞状细胞患者中的作用。这是评估AZD4547作为靶向治疗fgfr改变的鳞状细胞NSCLC患者的第一个II期试验，也是在这种疾病环境中成功实施和实施国家总方案的第一个示范。方法：符合条件的患者有肿瘤FGFR改变或突变，并且在至少一种以铂为基础的全身治疗后病情进展。患者口服AZD4547 80 mg，每日2次。主要终点是实体瘤1.1版应答评价标准的应答；次要终点包括无进展生存期、总生存期和反应持续时间（DoR）。结果：92例患者被分配到S1400D组，43例入组，27例azd4547治疗的患者可评估。可评估的患者主要是白人（n = 24, 89%），中位年龄66岁（49-88岁），女性（n = 7, 26%）。FGFR改变包括FGFR1扩增（n = 23; 85%）、FGFR3扩增（n = 2; 7%）、FGFR3 S249C （n = 2; 7%）和FGFR3融合（n = 1; 4%）。ADZ4547治疗耐受性良好；6例患者发生3级不良事件，1例患者发生4级败血症。在27例反应可评估的患者中，1例FGFR3 S249C患者有未证实的部分缓解，DoR为1.5个月，1例FGFR1扩增患者有证实的部分缓解，DoR为2.9个月（7%，95%可信区间[CI]: 0%-17%）。azd4547治疗组的中位无进展生存期和总生存期分别为2.7个月（95% CI: 1.4-4.5个月）和7.5个月（95% CI: 3.7-9.3个月）。结论：AZD4547在这个主要是FGFR1/ fgfr3扩增的队列中具有可接受的安全性，但活性很小。Lung-MAP中其他靶向药物的评估正在进行中。(C) 2019年国际肺癌研究协会。Elsevier Inc.出版。版权所有。
Background: S1400D is a biomarker-driven therapeutic substudy of Lung-MAP evaluating the fibroblast growth factor (FGF) receptor (FGFR) inhibitor AZD4547 in patients with FGF pathway-activated squamous cell. This is the first phase II trial to evaluate AZD4547 as a targeted approach in patients with previously treated FGFR-altered squamous cell NSCLC and is the first demonstration of successful implementation and conduct of a national umbrella protocol in this disease setting.Methods: Eligible patients had tumoral FGFR alteration or mutation and had progressive disease after at least one line of platinum-based systemic therapy. Patients received AZD4547 80 mg twice daily orally. Primary endpoint was response by Response Evaluation Criteria in Solid Tumors version 1.1; secondary endpoints included progression-free survival, overall survival, and duration of response (DoR).Results: Ninety-two patients were assigned to S1400D, 43 were enrolled, and 27 AZD4547-treated patients were evaluable. Evaluable patients were predominantly white (n = 24, 89%), median age 66 years (range, 49-88 years old), and female (n = 7, 26%). FGFR alterations included FGFR1 amplification (n = 23; 85%), FGFR3 amplification (n = 2; 7%), FGFR3 S249C (n = 2; 7%), and FGFR3 fusion (n = 1; 4%). Treatment with ADZ4547 was well tolerated; grade 3 adverse events occurred in six patients, and one patient had grade 4 sepsis. Of 27 response-evaluable patients, 1 patient with FGFR3 S249C had unconfirmed partial response with a DoR of 1.5 months and 1 patient with FGFR1 amplification had a confirmed partial response with a DoR of 2.9 months (7%, 95% confidence interval [CI]: 0%-17%). Median progression-free survival and overall survival for the AZD4547-treated cohort were 2.7 months (95% CI: 1.4-4.5 months) and 7.5 months (95% CI: 3.7-9.3 months).Conclusions: AZD4547 had an acceptable safety profile but minimal activity in this predominantly FGFR1/FGFR3amplified cohort. Evaluation of other targeted agents in Lung-MAP is ongoing. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.