title: A phase 2 trial of dasatinib in patients with advanced HER2-positive and/or hormone receptor-positive breast cancer.
abstract: OBJECTIVE
  SRC-family kinases (SFK) are involved in numerous oncogenic signaling pathways. A phase 2 trial of dasatinib, a potent oral tyrosine kinase inhibitor of SFKs, was carried out in patients with human epidermal growth factor receptor 2-positive (HER2+) and/or hormone receptor-positive (HR+) advanced breast cancer.
  
  
  METHODS
  Patients with measurable tumors and progression after chemotherapy and HER2 and/or HR-targeted agents in adjuvant or metastatic settings (maximum of two prior metastatic setting regimens) received twice daily dasatinib. Primary endpoint was Response Evaluation Criteria in Solid Tumors-defined response rate. Secondary endpoints included toxicity and limited pharmacokinetics.
  
  
  RESULTS
  Seventy patients (55 years median age) were treated, 83% of HER2+ patients had received prior HER2-directed therapy, and 61% of HR+ patients had received prior endocrine therapy in the advanced setting. Dasatinib starting dose was reduced from 100 to 70 mg twice daily to limit toxicity. Median therapy duration was 1.8 months in both dose groups and most discontinuations were due to progression. Of 69 evaluable patients, three had confirmed partial responses and six had stable disease for 16 weeks or more (disease control rate = 13.0%); all nine of these tumors were HR+ (two were also HER2+). The most common drug-related toxicities were gastrointestinal complaints, headache, asthenia, and pleural effusion. Grade 3-4 toxicity occurred in 37% of patients and was comparable between doses; drug-related serious adverse events were less frequent with 70 mg twice daily than 100 mg twice daily.
  
  
  CONCLUSIONS
  Limited single-agent activity was observed with dasatinib in patients with advanced HR+ breast cancer.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. Erica_Mayer@dfci.harvard.edu
authors: Erica L
authors: EL
authors: Mayer
authors: Jean-Francois
authors: JF
authors: Baurain
authors: Joseph
authors: J
authors: Sparano
authors: Lewis
authors: L
authors: Strauss
authors: Mario
authors: M
authors: Campone
authors: Pierre
authors: P
authors: Fumoleau
authors: Hope
authors: H
authors: Rugo
authors: Ahmad
authors: A
authors: Awada
authors: Oumar
authors: O
authors: Sy
authors: Antonio
authors: A
authors: Llombart-Cussac
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D000069439:Dasatinib; D005260:Female; D006801:Humans; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000069439:Dasatinib; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013844:Thiazoles; D019061:src-Family Kinases