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

Saracatinib is an oral, tyrosine kinase inhibitor selective for Src. This was a nonrandomized, open-label, phase II trial to evaluate the efficacy/safety of saracatinib monotherapy in patients with estrogen receptor (ER)- and progesterone receptor (PR)-negative, metastatic breast cancer (MBC). Nine patients were treated on study before the trial was closed to accrual at the investigators' request, based on the observed risk: benefit ratio. Based on this series, saracatinib does not appear to have significant single-agent activity for the treatment of patients with ER(-)/PR(-) MBC. 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)(-) metastatic breast cancer (MBC). Patients and Methods: Patients who had undergone <= 1 previous chemotherapy regimen for measurable ER- and PR- MBC 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 (PFS). Levels of circulating tumor cells (CTCs) 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 patient had achieved CR, PR, or SD > 6 months. The median time to treatment failure was 82 days (12-109 days). The majority (89%) of patients discontinued saracatinib because of disease progression. One patient acquired potentially treatment-related grade 4 hypoxia with interstitial infiltrates and was removed from the study. Common adverse events included fatigue, elevated liver enzymes, 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- MBC.