Role of pazopanib (PZ) in modulating hormone resistance in advanced breast cancer (ABC).

529 Background: Hormone resistance develops in nearly all patients (pts) with hormone receptor positive (HR+) ABC. Preclinical data suggests that higher levels of vascular endothelial growth factor (VEGF) are associated with hormone resistance. We conducted a phase II trial to evaluate the clinical benefit (CB) from adding PZ, a VEGF receptor tyrosine kinase inhibitor (TKI) to a nonsteroidal aromatase inhibitor (NSAI) in pts with ABC progressing on NSAIs. Methods: Eligibility included postmenopausal women with HR+ ABC and evidence of progressive disease after at least one month of NSAI therapy. Treatment was PZ 800 mg/day plus either letrozole or anastrozole. The primary endpoint was CB rate (CBR) at 12 weeks (wks). Secondary endpoints were progression free survival (PFS) and safety. A CBR of 20% was considered a clinically meaningful comparison to the expected CBR of < 5% with continued therapy after progression on an NSAI. Using a 2 stage design, stable disease in at least one of the first 13 pts allowe...