• Matthew I Milowsky, Christian Dittrich, Ignacio Durán, Satinder Jagdev, Frederick E Millard, Christopher J Sweeney, Dean Bajorin, Linda Cerbone, David I Quinn, Walter M Stadler, Jonathan E Rosenberg, Melissa Lochheed, Paramita Sen, Matthew Squires, Michael Shi, and Cora N Sternberg.
• Department of Medicine, Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. Electronic address: matt_milowsky@med.unc.edu.
• Eur. J. Cancer. 2014 Dec 1;50(18):3145-52.

BackgroundSecond-line treatment options for patients with advanced urothelial carcinoma (UC) are limited. Fibroblast growth factor receptor 3 (FGFR3) is dysregulated in UC by activating mutations or protein overexpression in non-mutant tumours. In this study, the efficacy, pharmacodynamics and safety of dovitinib-a broad-targeted inhibitor of tyrosine kinases, including FGFR3-were evaluated in patients with previously treated advanced UC with and without FGFR3 mutations.MethodsForty-four adults with advanced UC who had progressed after one to three platinum-based and/or combination chemotherapy regimens were classified as having mutant (FGFR3(MUT); n=12), wild-type (FGFR3(WT); n=31), or unknown (n=1) FGFR3 status. Patients received 500 mg dovitinib once daily on a 5-days-on/2-days-off schedule. The primary end-point of this two-stage study was the investigator-assessed overall response rate (ORR).ResultsMost of the patients were men (75%) and over half of the patients were aged ⩾65 years (61%). All patients had received ⩾1 prior antineoplastic therapy for UC. The study was terminated at the end of stage 1, when it was determined by investigator review that the ORR of both the FGFR3(MUT) (0%; 95% confidence interval [CI], 0.0-26.5) and FGFR3(WT) (3.2%; 95% CI, 0.1-16.7) groups did not meet the criteria to continue to stage 2. The most common grade 3/4 adverse events, suspected to be study-drug related, included thrombocytopenia (9%), fatigue (9%), and asthenia (9%).ConclusionAlthough generally well tolerated, dovitinib has very limited single-agent activity in patients with previously treated advanced UC, regardless of FGFR3 mutation status. clinicaltrials.gov NCT00790426.Copyright © 2014 Elsevier Ltd. All rights reserved.

34 keywords...

hide…