September 23, 2009 (Berlin, Germany) — Sorafenib (Nexavar) has shown promise in breast cancer in a phase 2b trial, and further studies are now planned.

The results were presented here at a presidential session of the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress.

Sorafenib added to capecitabine (Xeloda) significantly improved progression-free survival, compared with capecitabine alone, in locally advanced or metastatic breast cancer.

The fact that both drugs were administered orally "may represent a unique and convenient treatment option for patients with breast cancer," said principal investigator José Baselga, MD, professor of medicine at the Vall d'Hebron Institute of Oncology in Barcelona, Spain.

Sorafenib is currently indicated for use in renal cell carcinoma and hepatocellular carcinoma. It was tried in breast cancer because a number of recent studies have shown "clear evidence that the role of angiogenesis is critically important," Dr. Baselga explained.

Inhibition of angiogenesis has been shown to be beneficial in breast cancer in studies with bevacizumab (Avastin), which received accelerated approval from the US Food and Drug Administration for this indication.

Sorafenib is another step in this approach, but it is active on many more targets and is also an oral drug, noted Anne-Lisa Børresen-Dale, PhD, from the Norwegian Radium Hospital in Oslo. Bevacizumab is active against the vascular endothelial growth-factor (VEGF) receptor; sorafenib, in addition to inhibiting VEGF, acts on the platelet-derived growth-factor receptor and several other tyrosine kinases.

"This means that sorafenib offers a broader approach," Dr. Børresen-Dale told Medscape Oncology. This does not necessarily mean that it will have a bigger clinical impact, but "it is an interesting idea to test," she said, adding that the results so far have been "very promising."

Increase in Progression-Free Survival

The new study, known as SOLTI-0701, compared sorafenib plus capecitabine with capecitabine alone. Sorafenib 400 mg was given twice daily, and capecitabine1000 mg/m2 was given twice daily for 14 of every 21 days, which is the dose that is normally used in clinical practice and slightly lower than the dose that was approved (1250 mg/m2), Dr. Baselga explained.

The study was conducted in 229 patients with unresectable locally advanced or metastatic breast cancer (HER-negative), who had previously undergone only 1 course of or no chemotherapy.

Median progression-free survival was significantly higher in the combination group (6.4 vs 4.1 months for capecitabine alone; P = .0006), with a hazard ratio (HR) of 0.576 (95% confidence interval 0.410 - 0.809).

"This shows a 42% reduction in the risk of disease progression," Dr. Baselga said.

The difference in progression-free survival was statistically significant in patients who had not received any previous chemotherapy (first line HR, 0.498) and in those who had already received 1 previous regimen (second line HR, 0.652), he reported.

However, there was no significant difference in the overall response, and "we are still waiting for data on overall survival," he told meeting attendees.

There was a higher incidence of hand and foot syndrome in patients who were treated with the combination of sorafenib and capecitabine, and 15 patients (13.4%) taking the combination withdrew from the trial because of adverse effects, whereas only 9 patients (8%) taking capecitabine alone did.

But Dr. Baselga noted that the combination "was tolerable and the side effects were mostly manageable. No new or unexpected side effects were observed."

"The results suggest that sorafenib may be a valuable addition to chemotherapy in breast cancer," Dr. Baselga said.

The study was funded by Onyx and Bayer, the manufacturers of sorafenib.

15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstract 3LBA. Presented September 23, 2009.

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