Phase II Sorafenib Study Yields Positive Results

The addition of sorafenib to capecitabine as a first-line therapy for patients with advanced breast cancer resulted in a 42% reduction in the risk of disease progression or death among participants in a phase IIB trial, according to research reported at the Miami Breast Cancer Conference.

In one of the top posters presented at the conference, researchers said that the results warranted a phase III trial for sorafenib, an antiangiogenic and antiproliferative multikinase inhibitor. In fact, a phase 3 trial was launched in February.

Lead investigator Patricia Gómez, MD, an attending physician and senior clinical investigator at the Hospital Vall d’Hebron, Barcelona, Spain, said the research team wanted to examine how the addition of a targeted therapeutic agent would impact conventional therapy. She said they chose sorafenib because of its antiangiogenic qualities and because patients can take it orally.

Until now, sorafenib (Nexavar), which was approved by the FDA in 2005, has been used only for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma. However, the SOLTI-0701 multinational, double-blind study enrolled 229 patients with advanced HER2-negative breast cancer previously treated with ≤1 prior chemotherapy regimens. Patients were randomized virtually 1:1 to sorafenib with capecitabine or placebo with capecitabine. Progression-free survival (PFS) was the primary endpoint of the study.

As first-line therapy, PFS for patients in the sorafenib arm was 7.6 months, compared with 4.1 months for those in the placebo group. Gómez said that was the most significant finding of the study.

As second-line therapy, sorafenib made a measurable but not statistically significant difference, improving median PFS to 5.7 months compared with 4.1 months for the placebo group.

In overall survival (OS), a secondary endpoint, the median OS for the sorafenib arm was 22.9 months, compared with 20.9 months for the placebo arm.

Gómez said the most significant adverse effect in the sorafenib arm was hand-foot skin reaction, with 44% of patients reporting grade 3 symptoms. She felt those symptoms could be managed.

The study is 1 of 4 phase IIB trials studying the combination of sorafenib with other therapies as part of the TIES (Trials to Investigate the Effects of Sorafenib) breast cancer program.