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摘要
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 (18)FDG-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.
- 出版日期2017-8-1
