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

Mavratzas A, Baek S, Gerber B, Schmidt M, Moebus , Foerster F, Grischke EM, Fasching P, Strumberg D, Solomayer E, Klare P, Windemuth-Kieselbach C, Hartmann S, Schneeweiss A, Marine F (2019)


Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 45

Pages Range: 22-28

DOI: 10.1016/j.breast.2019.02.002

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.

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APA:

Mavratzas, A., Baek, S., Gerber, B., Schmidt, M., Moebus, ., Foerster, F.,... Marine, F. (2019). 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. BREAST , 45, 22-28. https://dx.doi.org/10.1016/j.breast.2019.02.002

MLA:

Mavratzas, A., et al. "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." BREAST 45 (2019): 22-28.

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