Phase II Trial of Saracatinib (AZD0530), an Oral SRC-inhibitor for the Treatment of Patients with Hormone Receptor-negative Metastatic Breast Cancer

Abstract

Background Src activation is associated with cell migration, proliferation and metastasis. Saracatinib is an oral, tyrosine kinase inhibitor (TKI) selective for Src. We performed this trial to evaluate the efficacy and safety of saracatinib monotherapy in patients with estrogen receptor (ER)- and progesterone receptor (PR)-negative, metastatic breast cancer. Patients and Methods Patients with ≤1 prior chemotherapy regimen for measurable, ER- and PR-negative metastatic breast cancer received saracatinib 175 mg orally daily. The primary endpoint was disease control defined as complete response (CR) + partial response (PR) + stable disease (SD) >6 months. Secondary endpoints included toxicity and progression-free survival. Levels of circulating tumor cells in response to therapy were measured over time. Results Nine patients were treated on study. After a median of 2 cycles (range 1–3), no patients achieved CR, PR, or SD >6 months. The median time to treatment failure was 82 days (12–109).The majority (89%) of patients discontinued saracatinib because of disease progression. One patient developed potentially treatment-related grade 4 hypoxia with interstitial infiltrates and was removed from study. Common adverse events included fatigue, elevated liver chemistries, nausea, hyponatremia, dyspnea, cough, and adrenal insufficiency. Conclusions These efficacy results were not sufficiently promising to justify continued accrual to this study. Based on this series, saracatinib does not appear to have significant single-agent activity for the treatment of patients with ER(−)/PR(−) metastatic breast cancer.