Slides from a presentation at SABCS 2009 and transcribed comments from a recent interview with Adam M Brufsky, MD, PhD (12/23/09)

ADAM M BRUFSKY, MD, PhD: Gradishar and his colleagues examined the activity of sorafenib, a multitargeted tyrosine kinase inhibitor against VEGF, EGFR, VGFR1 and VGFR2, in advanced breast cancer. The idea behind this study is great, especially since we know that activity with sorafenib already exists in both renal cell and hepatocellular carcinoma. Therefore, it’s possible that sorafenib is also active in breast cancer.

This trial is part of the TIES program, a program comprising different trials investigating the efficacy of sorafenib worldwide. In this particular study, eligible patients need to have locally recurrent or metastatic breast cancer that must be HER2/neu-negative. The study design is straightforward, with 220 patients randomly assigned to first-line therapy with weekly paclitaxel at the ECOG-E2100 dose of 90 mg/m² with or without sorafenib.

Interestingly, the difference in progression-free survival (PFS) between the two arms was not statistically significant. As a result, a subgroup analysis was performed to see if one group deviated wildly from the others, but none were identified. The secondary endpoint of time to disease progression seemed to illustrate more of a benefit with the combination arm: 8.1 months compared to 5.6 months. But one must be cautious when evaluating these trials in which the endpoint chosen to depict the data is a little outside of the primary endpoint. The response rate also seemed to be higher with the sorafenib arm: 67 versus 54 percent. Regarding adverse events, the major issue observed was hand-foot syndrome, which is often seen in sorafenib trials.

Overall, this study indicates potential trends toward improvement in efficacy with the addition of sorafenib to paclitaxel. The only difference between this study and previous trials is that this is a large, randomized, Phase II experience. Appropriately, the investigators suggest that this could lead to a large Phase III study. But I don’t believe there is a take-home message for the practicing oncologist quite yet. Personally, I would not use sorafenib with paclitaxel as first-line therapy just yet.

Dr Brufsky is Associate Professor of Medicine and Associate Division Chief of Hematology/Oncology at the University of Pittsburgh, Co-Director of the Comprehensive Breast Cancer Center and Associate Director for Clinical Investigation at the University of Pittsburgh Cancer Institute in Pittsburgh, Pennsylvania.