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Breast. 2019 Feb 13;45:22-28. doi: 10.1016/j.breast.2019.02.002. [Epub ahead of print]

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.

Author information

1
National Center for Tumor Disease, Gynecologic Oncology, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: athanasios.mavratzas@med.uni-heidelberg.de.
2
National Center for Tumor Disease, Gynecologic Oncology, University Hospital Heidelberg, Heidelberg, Germany.
3
Department of Obstetrics and Gynecology, University Hospital Rostock, Rostock, Germany.
4
Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany.
5
Department of Obstetrics and Gynecology, Hospital Frankfurt Hoechst, Frankfurt, Germany.
6
Gynecologic-oncologic Medical Care Center Chemnitz, Chemnitz, Germany.
7
Department of Obstetrics and Gynecology, University Tuebingen, Tuebingen, Germany.
8
Department of Obstetrics and Gynecology, University Hospital Erlangen, Erlangen, Germany.
9
Department of Internal Medicine, Hematology and Oncology, Marien Hospital Herne, Herne, Germany.
10
Department of Obstetrics and Gynecology, University Saarland, Homburg, Germany.
11
Oncologic Medical Care Center Krebsheilkunde, Berlin, Germany.
12
Alcedis GmbH, Giessen, Germany.

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/m2 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/m2 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.

KEYWORDS:

Antiangiogenic agents; Docetaxel; Metastatic breast cancer; Sorafenib

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