A phase III trial of Nexavar tablets in patients with advanced breast cancer did not meet its primary endpoint of extending progression-free survival.
The study, called RESILIENCE, evaluated Nexavar (sorafenib) in combination with capecitabine compared to capecitabine plus placebo in patients with HER2-negative breast cancer who are resistant to or have failed prior taxane therapy, and resistant to or failed anthracycline or for whom further anthracycline therapy is not indicated.
Based on initial review of the data, the types of adverse events observed were generally comparable with those known for either sorafenib or capecitabine. Data from this study are expected to be presented at an upcoming scientific congress, according to the drug’s sponsors, Bayer HealthCare and Onyx Pharmaceuticals Inc.
RESILIENCE was a randomized, double-blind study that enrolled 537 patients in more than 20 countries.
Secondary endpoints of the trial included overall survival, time to progression, overall response rate, disease control rate, duration of response, patient reported quality of life and safety.
Patients were randomized to receive either 600 mg of oral sorafenib or matching placebo daily on a continuous schedule, in addition to 1,000 mg/m(2) of capecitabine twice daily for 14 days of a 21 day cycle.
Nexavar is approved in the U.S. for the treatment of patients with unresectable hepatocellular carcinoma, patients with advanced renal cell carcinoma and patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.
It is thought to inhibit both the tumor cell and tumor vasculature. In in vitro studies, Nexavar has been shown to inhibit multiple kinases thought to be involved in both cell proliferation and angiogenesis. These kinases include Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.
Phase II ThermoDox Trial Demonstrates Positive Response
Interim data from an ongoing open-label phase II trial of ThermoDox in recurrent chest wall breast cancer demonstrated positive local response rates in combination with mild hyperthermia.
The trial, named DIGNITY, is designed to enroll 20 patients at several U.S. clinical sites—of the 13 patients enrolled and treated, 10 were eligible for evaluation of efficacy.
Sixty percent of patients experienced a stabilization of highly refractory disease with a local response rate of 50 percent, notably three complete responses, two partial responses and one patient with stable disease.
These data are consistent with the previously reported positive phase I data in RCWBC.
Celsion Corporation, the drug’s sponsor, previously reported combined clinical data from two phase I trials, the phase 1 DIGNITY study and the Duke University-sponsored phase I trial of ThermoDox plus hyperthermia in RCWBC.
“In this population, tumor response is a clinically meaningful endpoint,” said Nicholas Borys, Celsion’s senior vice president and chief medical officer. “Unchecked, progression of recurrent chest wall lesions results in severe and debilitating complications.”
