title: 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)(-) metastatic breast cancer (MBC).
  
  
  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.
authors: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors: Ayca
authors: A
authors: Gucalp
authors: Joseph A
authors: JA
authors: Sparano
authors: James
authors: J
authors: Caravelli
authors: Jean
authors: J
authors: Santamauro
authors: Sujata
authors: S
authors: Patil
authors: Alyson
authors: A
authors: Abbruzzi
authors: Christine
authors: C
authors: Pellegrino
authors: Jackie
authors: J
authors: Bromberg
authors: Chau
authors: C
authors: Dang
authors: Maria
authors: M
authors: Theodoulou
authors: Joan
authors: J
authors: Massague
authors: Larry
authors: L
authors: Norton
authors: Clifford
authors: C
authors: Hudis
authors: Tiffany A
authors: TA
authors: Traina
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009519:New York City; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C515233:saracatinib; D011505:Protein-Tyrosine Kinases