title: A Phase II Study of Dovitinib in Patients with Recurrent or Metastatic Adenoid Cystic Carcinoma.
abstract: Purpose:Genetic and preclinical studies have implicated FGFR signaling in the pathogenesis of adenoid cystic carcinoma (ACC). Dovitinib, a suppressor of FGFR activity, may be active in ACC.Experimental Design:In a two-stage phase II study, 35 patients with progressive ACC were treated with dovitinib 500 mg orally for 5 of 7 days continuously. The primary endpoints were objective response rate and change in tumor growth rate. Progression-free survival, overall survival, metabolic response, biomarker, and quality of life were secondary endpoints.Results:Of 34 evaluable patients, 2 (6%) had a partial response and 22 (65%) had stable disease >4 months. Median PFS was 8.2 months and OS was 20.6 months. The slope of the overall TGR fell from 1.95 to 0.63 on treatment (P< 0.001). Toxicity was moderate; 63% of patients developed grade 3-4 toxicity, 94% required dose modifications, and 21% stopped treatment early. An early metabolic response based on18FDG-PET scans was seen in 3 of 15 patients but did not correlate with RECIST response.MYBgene translocation was observed and significantly correlated with overexpression of MYB but did not correlate with FGFR1 phosphorylation or clinical response to dovitinib.Conclusions:Dovitinib produced few objective responses in patients with ACC but did suppress the TGR with a PFS that compares favorably with those reported with other targeted agents. Future studies of more potent and selective FGFR inhibitors in biomarker-selected patients will be required to determine whether FGFR signaling is a valid therapeutic target in ACC.Clin Cancer Res; 23(15); 4138-45. ©2017 AACR.
authors.affiliation: UVA Cancer Center at the University of Virginia, Charlottesville, Virginia. PMD5B@hscmail.mcc.virginia.edu cythomas@wakehealth.edu.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Dillon
authors.affiliation: UVA Cancer Center at the University of Virginia, Charlottesville, Virginia.
authors.forename: Gina R
authors.initials: GR
authors.lastname: Petroni
authors.affiliation: UVA Cancer Center at the University of Virginia, Charlottesville, Virginia.
authors.forename: Bethany J
authors.initials: BJ
authors.lastname: Horton
authors.affiliation: UVA Cancer Center at the University of Virginia, Charlottesville, Virginia.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Moskaluk
authors.affiliation: UVA Cancer Center at the University of Virginia, Charlottesville, Virginia.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Fracasso
authors.affiliation: UVA Cancer Center at the University of Virginia, Charlottesville, Virginia.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Douvas
authors.affiliation: UVA Cancer Center at the University of Virginia, Charlottesville, Virginia.
authors.forename: Nikole
authors.initials: N
authors.lastname: Varhegyi
authors.affiliation: UVA Cancer Center at the University of Virginia, Charlottesville, Virginia.
authors.forename: Snjezana
authors.initials: S
authors.lastname: Zaja-Milatovic
authors.affiliation: Wake Forest University, Winston-Salem, North Carolina. PMD5B@hscmail.mcc.virginia.edu cythomas@wakehealth.edu.
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D020626:Oncogene Proteins v-myb / Q000235:genetics; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics
chemical_list: C500007:4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; D001562:Benzimidazoles; D020626:Oncogene Proteins v-myb; D015363:Quinolones; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1