Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer.
Springer Science and Business Media LLC
MetadataShow full item record
Coombes, R., Badman, P., Lozano-Kuehne, J., Liu, X., Macpherson, I., Zubairi, I., Baird, R., et al. (2022). Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer.. Nat Commun, 13 (1. 3246), 3246. https://doi.org/10.1038/s41467-022-30666-0
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.
Antineoplastic Agents, Benzamides, Breast Neoplasms, Female, Humans, Piperazines, Pyrazoles, Treatment Outcome
External DOI: https://doi.org/10.1038/s41467-022-30666-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338357
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: email@example.com