Sorafenib in combination with docetaxel as first-line therapy for HER2-negative metastatic breast cancer: Final results of the randomized, double-blind, placebo-controlled phase II MADONNA study. (June 2019)

• Record Type: Journal Article
• Authors: Mavratzas, A.; Baek, S.; Gerber, B.; Schmidt, M.; Moebus, V.; Foerster, F.; Grischke, E.M.; Fasching, P.; Strumberg, D.; Solomayer, E.; Klare, P.; Windemuth-Kieselbach, C.; Hartmann, S.; Schneeweiss, A.; Marmé, F.
• Is Part Of: Breast. Volume 45(2019)
• Page Start: 22
• Page End: 28
• Publication Date: 2019-06
• Subjects: Metastatic breast cancer -- Docetaxel -- Antiangiogenic agents -- Sorafenib; Breast -- Diseases -- Periodicals; Breast -- Tumors -- Periodicals; Breast -- Periodicals; Electronic journals; Periodicals; 616
• DOI: 10.1016/j.breast.2019.02.002
• Languages: English
• ISSNs: 0960-9776

Abstract

Abstract: Background: This multicenter, double-blind phase II study assessed the antitumor activity and toxicity profile of docetaxel with the antiangiogenic multikinase inhibitor sorafenib or matching placebo as a first-line treatment in patients with metastatic or locally advanced HER2-negative breast cancer. Patients and methods: Patients were randomized 1:1 to receive docetaxel 100 mg/m 2 on day 1 every 3 weeks in combination with sorafenib 400 mg bid or placebo on days 2–18 of each cycle until tumor progression, or unacceptable toxicity. Sorafenib/placebo could be continued at the investigator's discretion if docetaxel was stopped due to toxicity. Primary endpoint was progression free survival (PFS). Results: From October 2008 to December 2013, 102 patients were randomized; 98 patients were evaluable. The trial was prematurely terminated due to slow accrual. Due to increased toxicity the dose of docetaxel was reduced to 75 mg/m 2 and an increasing sorafenib dosing schedule was implemented as part of a protocol amendment. The addition of sorafenib to docetaxel did not improve PFS (8.2 vs. 7.3 months for docetaxel/placebo; HR 0.84, log rank p = 0.43 ), but led to higher rates of early treatment discontinuation. There were no statistically significant differences between sorafenib dosing schedules. Conclusions: Addition of sorafenib to taxane-based first-line chemotherapy in patients with metastatic breast cancer failed to improve PFS and resulted in increased toxicity. Highlights: Multicenter double-blind phase II MADONNA trial evaluated antitumor activity and toxicity of docetaxel and sorafenib or matching placebo as a 1 st line treatment in metastatic/locally advanced HER-2 negative breast cancer. Increased hematological and skin toxicity led to slow patient accrual and early trail termination. The trial failed to demonstrate improved PFS under addition of sorafenib to taxane-based chemotherapy in metastatic breast cancer.