Pazopanib in Combination With Capecitabine in Patients With Metastatic Breast Cancer
Status:
Completed
Trial end date:
2014-05-01
Target enrollment:
Participant gender:
Summary
Angiogenesis is essential for the growth of large tumor. A number of anti-angiogenic agents
are currently under development. Bevacizumab, a humanised monoclonal antibody to vascular
endothelial growth factor (VEGF), has been shown to improve disease free survival in first
line metastatic breast cancer when associated with chemotherapy 1. Results of a randomised
phase II trial combining sorafenib, a tyrosine kinase inhibitor targeting multiple tyrosine
kinases including VEGFR1, VEGFR2, VEGFR3, with capecitabine have recently been reported 2.
Compared to capecitabine plus placebo, progression-free survival in the capecitabine +
sorafenib arm was significantly increased from 4.1 months to 6.4 months. Toxicities were also
increased, with an incidence rate of grade 3/4 hand foot syndrome of 45% in the capecitabine
+ sorafenib arm compared to 13% in the capecitabine + placebo arm. The increased toxicity
will most likely limit the clinical use of this regimen.
Pazopanib is a potent, multi-targeted TKI of VEGFR-1, -2, -3, PDGFR-α and -β and c-kit and
has recently been approved for the treatment of renal cell cancer in the U.S. In the EU, a
positive opinion has been issued by the European Medicines Agency.
A phase II study of GW786034 (pazopanib) in patients with recurrent or metastatic invasive
breast carcinoma included 19 patients after a maximum of 2 lines of chemotherapy for advanced
disease 3. Pazopanib 800 mg daily was given continuously.
A clinically significant rate of stable disease (58%) was detected with a median TTP of 5.3
months (95% CI: 1.8 - 9.0 months). Four patients treated with pazopanib had SD for ≥ 6
months, for a clinical benefit rate (CBR), defined as rate of SD for ≥ 6 months or CR or PR,
of 5/19 (26%), which is at least comparable to sunitinib and bevacizumab (CBR 16% and 17%,
respectively).
The pivotal study of full dose (800 mg) daily pazopanib in renal cell cancer reported hand
foot syndrome of all grades in only 6% of patients 4. The optimally tolerated regimen (OTR)
of pazopanib was determined when administered in combination with capecitabine and
oxaliplatin in patients with advanced CRC 5. In patients who received capecitabine (850 mg
twice daily) plus 800 mg once daily pazopanib combined with oxaliplatin, the incidence of
hand foot syndrome of all grades was 24%.
The present study will investigate the combination of pazopanib and capecitabine in advanced
or metastatic breast cancer with the aim to develop a new treatment option with increased
efficacy and tolerability.