Oswald, AJ, Symeonides, SN, Wheatley, D, Chan, S, Brunt, AM, McAdam, K, Schmid, P, Waters, S, Poole, C, Twelves, C, Perren, T, Bartlett, J, Piper, T, Chisholm, EM, Welsh, M, Hill, R, Hopcroft, LEM, Barrett-Lee, P and Cameron, DA (2023) Aromatase inhibition plus/minus Src inhibitor saracatinib (AZD0530) in advanced breast cancer therapy (ARISTACAT): a randomised phase II study. Breast Cancer Research and Treatment.

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PURPOSE: The development of oestrogen resistance is a major challenge in managing hormone-sensitive metastatic breast cancer. Saracatinib (AZD0530), an oral Src kinase inhibitor, prevents oestrogen resistance in animal models and reduces osteoclast activity. We aimed to evaluate the efficacy of saracatinib addition to aromatase inhibitors (AI) in patients with hormone receptor-positive metastatic breast cancer. METHODS: This phase II multicentre double-blinded randomised trial allocated post-menopausal women to AI with either saracatinib or placebo (1:1 ratio). Patients were stratified into an "AI-sensitive/naïve" group who received anastrozole and "prior-AI" group who received exemestane. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and toxicity. RESULTS: 140 patients were randomised from 20 UK centres to saracatinib/AI (n = 69) or placebo/AI (n = 71). Saracatinib was not associated with an improved PFS (3.7 months v. 5.6 months placebo/AI) and did not reduce likelihood of bony progression. There was no benefit in OS or ORR. Effects were consistent in "AI-sensitive/naive" and "prior-AI" sub-groups. Saracatinib was well tolerated with dose reductions in 16% and the main side effects were gastrointestinal, hypophosphatemia and rash. CONCLUSION: Saracatinib did not improve outcomes in post-menopausal women with metastatic breast cancer. There was no observed beneficial effect on bone metastases. CRUKE/11/023, ISRCTN23804370.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Uncontrolled Keywords: Hormone receptor-positive breast cancer; Endocrine resistance; Src; Bone metastasis
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine and Health Sciences > School of Medicine
Related URLs:
Depositing User: Symplectic
Date Deposited: 28 Mar 2023 13:59
Last Modified: 28 Mar 2023 13:59
URI: https://eprints.keele.ac.uk/id/eprint/12098

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