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Aromatase inhibition plus/minus Src inhibitor saracatinib (AZD0530) in advanced breast cancer therapy (ARISTACAT): a randomised phase II study.

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; Cameron, DA

Aromatase inhibition plus/minus Src inhibitor saracatinib (AZD0530) in advanced breast cancer therapy (ARISTACAT): a randomised phase II study. Thumbnail


AJ Oswald

SN Symeonides

D Wheatley

S Chan

K McAdam

P Schmid

S Waters

C Poole

C Twelves

T Perren

J Bartlett

T Piper

EM Chisholm

M Welsh

R Hill

LEM Hopcroft

P Barrett-Lee

DA Cameron


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.

Journal Article Type Article
Acceptance Date Jan 31, 2023
Publication Date Mar 2, 2023
Journal Breast Cancer Research and Treatment
Print ISSN 0167-6806
Electronic ISSN 1573-7217
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 199
Keywords Hormone receptor-positive breast cancer; Endocrine resistance; Src; Bone metastasis
Publisher URL