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Updated: Aug 8, 2025

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
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Aromatase inhibition plus/minus Src inhibitor saracatinib (AZD0530) in advanced breast cancer therapy (ARISTACAT): a

Ailsa J Oswald1, Stefan N Symeonides2, Duncan Wheatley3

  • 1University of Edinburgh, Edinburgh, Scotland, UK. ailsa.oswald@ed.ac.uk.

Breast Cancer Research and Treatment
|March 1, 2023
PubMed
Abstract

Insights

Adding saracatinib to aromatase inhibitors did not improve progression-free survival for metastatic breast cancer patients. This Src kinase inhibitor showed no benefit for bone metastases or overall survival in the trial.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Oestrogen resistance is a key challenge in hormone-sensitive metastatic breast cancer.
  • Saracatinib, a Src kinase inhibitor, showed promise in preclinical models for overcoming oestrogen resistance and reducing osteoclast activity.

Purpose of the Study:

  • To evaluate the efficacy of adding saracatinib to aromatase inhibitors (AI) in post-menopausal women with hormone receptor-positive metastatic breast cancer.
  • To assess the impact of saracatinib on progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and bone metastases.

Main Methods:

  • A phase II multicentre, double-blinded, randomised trial involving 140 post-menopausal women.
  • Patients received either AI with saracatinib or AI with placebo in a 1:1 ratio.
  • Stratification into "AI-sensitive/naïve" (anastrozole) and "prior-AI" (exemestane) groups.

Main Results:

  • Saracatinib did not improve PFS (3.7 months vs. 5.6 months with placebo/AI) or reduce bony progression.
  • No significant benefit was observed in overall survival (OS) or objective response rate (ORR).
  • The drug was well tolerated, with common side effects including gastrointestinal issues, hypophosphatemia, and rash.

Conclusions:

  • Saracatinib addition to aromatase inhibitors did not improve clinical outcomes in metastatic breast cancer.
  • No beneficial effect on bone metastases was observed with saracatinib treatment.
  • The study did not support the use of saracatinib in this patient population.
Keywords:
Bone metastasisEndocrine resistanceHormone receptor-positive breast cancerSrc

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