期刊
JOURNAL OF THORACIC ONCOLOGY
卷 14, 期 10, 页码 1847-1852出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtho.2019.05.041
关键词
LUNG-MAP; SWOG1400; FGFR inhibitor
资金
- National Institutes of Health/National Cancer Institute [CA180888, CA180819, CA180820, CA180821, CA180868, CA18 9858, CA189861, CA189830, CA189821, CA180858, CA189971, CA189972, CA180826, CA189822, CA180798]
- Amgen through the Foundation for the National Institutes of Health
- Astra Zeneca through the Foundation for the National Institutes of Health
- Bristol-Myers Squibb Company through the Foundation for the National Institutes of Health
- Genentech through the Foundation for the National Institutes of Health
- Pfizer through the Foundation for the National Institutes of Health
- Friends of Cancer Research
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.
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