Imperial College London
Alternate

ProfessorCharlesCoombes

Faculty of Medicine, Department of Surgery & Cancer

Emeritus Professor of Medical Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2135c.coombes

 
 
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Assistant

 

Mrs Suzy Ford +44 (0)20 7594 2135

 
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Location

 

145ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Coombes:2022:10.1038/s41467-022-30666-0,
author = {Coombes, R and Badman, P and Lozano-Kuehne, JP and Liu, X and Macpherson, IR and Baird, RD and Rosenfeld, N and Garcia-Corbacho, J and Cresti, N and Plummer, R and Armstrong, A and Allerton, R and Landers, D and Nicholas, H and McLellan, L and Lim, A and Mouliere, F and Pardo, OP and Seckl, MJ},
doi = {10.1038/s41467-022-30666-0},
journal = {Nature Communications},
title = {Results of the Phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer},
url = {http://dx.doi.org/10.1038/s41467-022-30666-0},
volume = {13},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - We conducted a phase IIa, multi-centre, open label, single arm study (RADICAL; NCT01791985) of AZD4547 (a potent and selective inhibitor of Fibroblast Growth Factor Receptor (FGFR)-1, 2 and 3 receptor tyrosine kinases) administered with anastrozole or letrozole in estrogen receptor positive metastatic breast cancer patients who had become resistant to aromatase inhibitors. After a safety run-in study to assess safety and tolerability, we recruited 52 patients. The primary endpoint was change in tumour size at 12 weeks, and secondary endpoints were to assess response at 6 weeks, 20 weeks and every 8 weeks thereafter and tolerability of the combined treatment. Two partial responses (PR) and 19 stable disease (SD) patients were observed at the 12-week time point. At 28 weeks, according to centrally reviewed Response Evaluation Criteria in Solid Tumours (RECIST) criteria, five PR and 8 SD patients were observed in 50 assessable cases. Overall, objective response rate (5 PR) was of 10%, meeting the pre-specified endpoint. Fourteen patients discontinued due to adverse events. Eleven patients had retinal pigment epithelial detachments which was asymptomatic and reversible in all but one patient. Exploratory ribonucleic acid sequencing (RNA-Seq) analysis was done on patients’ samples: 6 differentially-expressed-genes could distinguish those who benefited from the addition of AZD4547.
AU  - Coombes,R
AU  - Badman,P
AU  - Lozano-Kuehne,JP
AU  - Liu,X
AU  - Macpherson,IR
AU  - Baird,RD
AU  - Rosenfeld,N
AU  - Garcia-Corbacho,J
AU  - Cresti,N
AU  - Plummer,R
AU  - Armstrong,A
AU  - Allerton,R
AU  - Landers,D
AU  - Nicholas,H
AU  - McLellan,L
AU  - Lim,A
AU  - Mouliere,F
AU  - Pardo,OP
AU  - Seckl,MJ
DO  - 10.1038/s41467-022-30666-0
PY  - 2022///
SN  - 2041-1723
TI  - Results of the Phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-022-30666-0
UR  - http://hdl.handle.net/10044/1/97661
VL  - 13
ER  -
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