title: A phase II study of pazopanib in patients with recurrent or metastatic invasive breast carcinoma: a trial of the Princess Margaret Hospital phase II consortium.
abstract: OBJECTIVE
  Angiogenesis is an important hallmark of breast cancer growth and progression. Pazopanib, an oral small molecule inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and KIT, has activity across a range of solid tumors. We evaluated the activity of single-agent pazopanib in recurrent or metastatic breast cancer (MBC).
  
  
  METHODS
  Patients with recurrent breast cancer or MBC, treated with up to two prior lines of chemotherapy, were eligible to receive pazopanib, 800 mg daily until progression. The primary endpoint was the objective response rate as measured by Response Evaluation Criteria in Solid Tumors. Secondary endpoints included time to progression, the stable disease rate, and toxicity. Using a two-stage design, confirmed response in three of 18 patients was required to proceed to stage 2.
  
  
  RESULTS
  Twenty evaluable patients were treated, with a median age of 56 years; 70% were estrogen receptor positive, all were human epidermal growth factor receptor 2 negative. The majority had one or two prior lines of chemotherapy. One patient (5%) had a partial response, 11 (55%) had stable disease (SD) [four (20%) with SD > or = 6 months], and seven (35%) had progressive disease as their best response. One (5%) was not evaluable. The median time to progression was 5.3 months. Pazopanib did not cause significant severe toxicity aside from grade 3-4 transaminitis, hypertension, and neutropenia in three patients each (14% each) and grade 3 gastrointestinal hemorrhage in one patient (5%).
  
  
  CONCLUSIONS
  Pazopanib provides disease stability in advanced breast cancer. The activity seen is comparable with that of other antiangiogenic agents in this setting. Pazopanib may be of interest for future studies in breast cancer, including in combination with other systemic agents.
authors.affiliation: 5-105 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Taylor
authors.forename: Stephen
authors.initials: S
authors.lastname: Chia
authors.forename: Susan
authors.initials: S
authors.lastname: Dent
authors.forename: Mark
authors.initials: M
authors.lastname: Clemons
authors.forename: Mark
authors.initials: M
authors.lastname: Agulnik
authors.forename: Pamela
authors.initials: P
authors.lastname: Grenci
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007191:Indazoles; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D066246:ErbB Receptors