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Eur J Cancer. 2014 Dec;50(18):3145-52. doi: 10.1016/j.ejca.2014.10.013. Epub 2014 Oct 30.

Phase 2 trial of dovitinib in patients with progressive FGFR3-mutated or FGFR3 wild-type advanced urothelial carcinoma.

Author information

1
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.
2
LBI-ACR VIEnna & ACR-ITR VIEnna, Center for Oncology and Haematology, Kaiser Franz Josef-Spital, Vienna, Austria.
3
Centro Integral Oncologico Clara Campal, Universidad CEU San Pablo, Madrid, Spain.
4
St. James's Institute of Oncology, Leeds, UK.
5
Department of Medicine, Division of Hematology-Oncology, University of California, San Diego, San Diego, CA, USA.
6
Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
7
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
8
Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
9
Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
10
Department of Medicine, University of Chicago, Chicago, IL, USA.
11
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
12
Novartis Pharma AG, Basel, Switzerland.

Abstract

BACKGROUND:

Second-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.

METHODS:

Forty-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).

RESULTS:

Most 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%).

CONCLUSION:

Although 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.

KEYWORDS:

Dovitinib; FGFR3; Fibroblast growth factor; Receptor tyrosine kinase; Urothelial carcinoma; VEGFR

PMID:
25457633
DOI:
10.1016/j.ejca.2014.10.013
[Indexed for MEDLINE]

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