| Autor: |
Aggarwal, Charu, Redman, Mary W., Lara, Primo N., Borghaei, Hossein, Hoffman, Philip, Bradley, Jeffrey D., Newman, Alfred J., Feldman, Marvin J., Minichiello, Katherine, Miao, Jieling, Mack, Philip C., Papadimitrakopoulou, Vassiliki A., Herbst, Roy S., Kelly, Karen, Gandara, David R. |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
J Thorac Oncol |
| Popis: |
BACKGROUND: S1400D is a biomarker-driven therapeutic sub-study of Lung-MAP evaluating the fibroblast growth factor receptor (FGFR) inhibitor AZD4547 in patients with FGF pathway-activated squamous cell non-small cell lung cancer (SqNSCLC). This is the first phase II trial to evaluate AZD4547 as a targeted approach in patients with previously treated FGFR-altered SqNSCLC 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 1 line of platinum-based systemic therapy. Patients received AZD4547 80 mg twice daily orally. Primary endpoint was response by RECIST 1.1; secondary endpoints included progression-free survival (PFS), overall survival (OS) 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 y (49–88), 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 (AEs) were seen in six patients; one patient had Grade 4 sepsis. Of 27 response evaluable patients, one patient with FGFR3 S249C had unconfirmed partial response with DoR of 1.5 months and one patient with FGFR1 amplification had a confirmed partial response with DoR of 2.9 months (7%, 95% CI 0–17%). Median PFS and OS for the AZD4547–treated cohort were 2.7 mos (95% CI 1.4 – 4.5 mos) and 7.5 mos (95% CI 3.7–9.3 mos). CONCLUSIONS: AZD4547 had an acceptable safety profile but minimal activity in this predominantly FGFR 1/3 amplified cohort. Evaluation of other targeted agents in Lung-MAP is currently ongoing. ClinicalTrials.gov Identifier |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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