Progression-free Survival Significantly Improved in Breast Cancer Patients on Sorafenib

Sorafenib (Nexavar) significantly improved progression-free survival in patients with breast cancer, according to the results of the SOLTI-0701 study presented at the ECCO 15 — ESMO 34 Joint Congress by José Baselga, MD, ESMO president and a member of the ECCO executive committee, and head of oncology, Vall d’Hebron University Hospital, Barcelona, Spain. According to Dr Baselga, “this is the first, large, randomized study that demonstrates significant clinical activity of sorafenib in breast cancer when given in combination with chemotherapy.”

Dr Baselga and his colleagues from Spain, France, and Brazil conducted SOLTI-0701, a double-blind, randomized, phase IIb clinical trial, which enrolled 229 patients with locally advanced or metastatic breast cancer between June 2007 and December 2008. All patients had HER-2 negative tumors and had undergone less than two previous chemotherapy regimens for advanced or metastatic breast cancer; individuals with active brain metastasis were excluded. Patients were randomized 1:1 to receive oral capecitabine (Xeloda) 1000 mg/m² twice daily for 14 of every 21 days plus a placebo (n = 114) or to capecitabine and oral sorafenib 400 mg twice daily continuously (n = 115).

The trial's initial results became available shortly before the ECCO 15 — ESMO 34 Joint Congress and showed an average progression-free survival of 6.4 months for women in the sorafenib arm compared with 4.1 months for those in the placebo arm (HR, 0.576; 95% CI, 0.410-0.809; P = .0006). “Our results showed that patients who received sorafenib plus capecitabine had a 74% improvement in the time they lived without their disease worsening compared to those who received the chemotherapy alone,” said Dr Baselga. “This is a very positive study and the magnitude of the benefit is such that it suggests that this agent will be an important addition to our therapeutic armory in breast cancer,” he added.

Overall survival data are not yet available; however, there was one death in the placebo arm, which was attributed to the side effects of capecitabine. In addition, 9 patients (8%) in the placebo arm and 15 (13.4%) in the sorafenib arm discontinued treatment due to adverse effects. Grade 3 or 4 toxicities for the placebo arm versus the sorafenib arm included hand-foot skin reactions (13% vs. 45%, respectively), diarrhea (5% for both arms), dyspnea (4% vs. 5%, respectively), neutropenia (3% vs. 5%, respectively), and mucositis (4% vs. 1%, respectively). The most common reasons for discontinuation included hand-foot skin reactions (2 in placebo arm vs. 8 in sorafenib arm) and diarrhea (3 in placebo arm vs. 1 in sorafenib arm).

“The regimen was tolerable and the side effects were mostly manageable. No new or unexpected side effects were observed with [the capecitabine and sorafenib] combination. The fact that this treatment could be taken orally may represent a unique and convenient treatment option for patients with breast cancer,” said Dr Baselga.

Based on the encouraging data from this trial, Onyx and Bayer are evaluating various strategies for sorafenib in breast cancer, and several other randomized, phase II studies of sorafenib in this setting are currently underway.

ECCO/ESMO Abstract 3LBA