A Phase II Study of Dovitinib in Patients with Recurrent or Metastatic Adenoid Cystic Carcinoma.

Abstract

<b>Purpose:</b> 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.<b>Experimental Design:</b> 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.<b>Results:</b> 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 (<i>P</i> < 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. <i>MYB</i> gene translocation was observed and significantly correlated with overexpression of MYB but did not correlate with FGFR1 phosphorylation or clinical response to dovitinib.<b>Conclusions:</b> 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. <i>Clin Cancer Res; 23(15); 4138-45. ©2017 AACR</i>.