TY - JOUR
T1 - A phase II study of dovitinib in patients with recurrent or metastatic adenoid cystic carcinoma
AU - Dillon, Patrick M.
AU - Petroni, Gina R.
AU - Horton, Bethany J.
AU - Moskaluk, Christopher A.
AU - Fracasso, Paula M.
AU - Douvas, Michael G.
AU - Varhegyi, Nikole
AU - Zaja-Milatovic, Snjezana
AU - Thomas, Christopher Y.
N1 - Funding Information:
The authors thank all of the patients and their families for their participation. We also thank the University of Virginia Cancer Center and the Adenoid Cystic Carcinoma Research Foundation. This study (NCT01524692) was funded by Novartis Pharmaceuticals. Some biomarker studies were supported by the UVA Cancer Center, Charlottesville, VA (to P.M. Dillon and C.A. Moskaluk). Statistical analysis was done by the Biostatistics Shared Resource, University of Virginia Cancer Center, University of Virginia (P30 CA044579). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Publisher Copyright:
©2017 AACR.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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 on 18FDG-PET scans was seen in 3 of 15 patients but did not correlate with RECIST response. MYB gene 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.
AB - 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 on 18FDG-PET scans was seen in 3 of 15 patients but did not correlate with RECIST response. MYB gene 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.
UR - http://www.scopus.com/inward/record.url?scp=85027175295&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-16-2942
DO - 10.1158/1078-0432.CCR-16-2942
M3 - Article
C2 - 28377480
AN - SCOPUS:85027175295
SN - 1078-0432
VL - 23
SP - 4138
EP - 4145
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -