NEW YORK (Reuters Health) – Adding sorafenib (Nexavar) to capecitabine (Xeloda) appears to improve progression-free survival in women with HER2-negative advanced breast cancer.
Phase IIb data were published online March 12 in the Journal of Clinical Oncology; based on those findings, the phase III RESILIENCE trial was designed and began enrollment in November 2010 (NCT01234337).
“RESILIENCE will provide definitive progression-free survival data for sorafenib plus capecitabine in advanced HER2-negative breast cancer and better characterize the benefit-to-risk profile of this treatment regimen,” said Dr. Jose Baselga from the Massachusetts General Hospital in Boston, in an email to Reuters Health.
Dr. Baselga, who led the phase IIb trial and is also involved in the phase III study, pointed out that sorafenib is already approved for treating renal cell carcinoma in more than 90 countries and hepatocellular carcinoma in more than 80 countries.
Sorafenib is an oral multikinase inhibitor with antiproliferative and antiangiogenic activity.
In the phase IIb trial, 229 women with HER2-negative adenocarcinoma of the breast and locally advanced (inoperable) or metastatic disease received capecitabine plus either sorafenib or placebo
Progression-free survival, the primary endpoint, was significantly longer with sorafenib plus capecitabine than with capecitabine alone (median 6.8 vs 4.1 months; p=0.001), which translated into a 42% reduction in the risk of disease progression or death.
The overall response rates did not differ significantly between the treatment groups. Overall survival did not appear to differ either, but the study wasn’t powered to analyze this endpoint.
Patients taking sorafenib had more rash, diarrhea, mucosal inflammation, neutropenia, and grade 2 hypertension, as well as more of the most common toxicity, hand-foot skin reaction/hand-foot syndrome.
Dose interruptions and reductions were more common with sorafenib.
While adding sorafenib to capecitabine achieved the primary endpoint of longer progression-free survival, the authors write, “the dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients.” Patients in the phase III trial, they add, are receiving a reduced sorafenib dose.
The trial was supported by Onyx Pharmaceuticals and Bayer Healthcare Pharmaceuticals, which also provided the sorafenib and editorial assistance.
J Clin Oncol 2012.