Sorafenib in the Treatment of Early Breast Cancer: Results of the Neoadjuvant Phase II Study - SOFIA.

BACKGROUND Sorafenib was tested for neoadjuvant treatment with an anthracycline/taxane-based chemotherapy in the open-label, multicentre, single-arm phase II study, 'SOFIA'. PATIENTS AND METHODS INCLUSION CRITERIA WERE: HER2 negative, cT3, cT4 or cT2 cN+, M0 primary breast cancer. Patients received 4 × epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) (EC) intravenously (i.v.) in 3-weekly cycles followed or preceded by 12 weeks of paclitaxel (Pw) 80 mg/m(2). In cohort 1, sorafenib started at 800 mg daily with chemotherapy. An initial daily sorafenib dose of 200 mg was escalated, based on individual toxicities, every 3 weeks in cohort 2 (starting with EC) and every 2 weeks in cohort 3 (starting with Pw). The primary objective was to identify the most feasible regimen; secondary objectives were safety, pathological complete response (pCR) at surgery and pharmacokinetics. RESULTS Of the 36 recruited patients, 7/12 patients completed the study in cohort 1 and 24/24 patients in cohorts 2 and 3. The median cumulative sorafenib dose per patient was 37%, 65% and 46% in cohorts 1, 2 and 3, respectively. The main grade 3-4 toxicities were neutropenia and hand-foot syndrome. The pCR (ypT0/is) rate was 27.7%. No pharmacokinetic interaction was observed between sorafenib and epirubicin. CONCLUSION Sorafenib EC-Pw is feasible if the starting dose is 200 mg, escalated every 3 weeks based on the patients' individual toxicities.