title: Phase II multicenter, uncontrolled trial of sorafenib  in patients with metastatic breast cancer.
abstract: This trial was conducted to assess the efficacy and safety of sorafenib in patients with metastatic breast cancer. In this multinational, open-label phase II study, patients with metastatic breast cancer that had progressed after at least one prior chemotherapy regimen were continuously treated with oral sorafenib, 400 mg twice daily. The primary endpoint was overall best response; a secondary endpoint was percentage of patients with stable disease for greater than or equal to 16 weeks. Biomarker analysis were also performed. Of the 56 patients enrolled into the study, 54 were treated with at least one dose of sorafenib. Partial response was observed in one patient (2%) and stable disease in 20 patients (37%); no complete responses were observed. Disease stabilization for greater than or equal to 16 weeks was seen in 12 patients (22%); stabilization for greater than or equal to 6 months in seven patients (13%). The most common drug-related grade 3 adverse events were rash/desquamation (6%), hand-foot skin reaction (4%), and fatigue (4%). Baseline vascular endothelial growth factor levels, levels of soluble epidermal growth factor receptor during treatment and both baseline and changes in soluble human epidermal growth factor receptor 2 levels correlated significantly with clinical outcomes. Although the primary endpoint of overall response rate showed minimal improvement on sorafenib 400 mg twice-daily treatment, the rate of disease stabilization was encouraging in patients treated with one or more lines of chemotherapy. The treatment had a clinically manageable toxicity profile. Further investigation of single-agent sorafenib in this patient population is not recommended; however, studies investigating combinations of sorafenib with chemotherapeutic agents are warranted and ongoing.
authors.affiliation: Fondazione IRCCS Istituto Tumori di Milano, Via Venezian, 1, 20133 Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bianchi
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamagni
authors.forename: Stefania
authors.initials: S
authors.lastname: Salvagni
authors.forename: Guenter
authors.initials: G
authors.lastname: Raab
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.forename: Nicole
authors.initials: N
authors.lastname: Laferriere
authors.forename: Carol
authors.initials: C
authors.lastname: Peña
authors.forename: Chetan
authors.initials: C
authors.lastname: Lathia
authors.forename: Loredana
authors.initials: L
authors.lastname: Bergamini
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D066246:ErbB Receptors