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
| Autor: | Martina Schmidt, Erich-Franz Solomayer, Bernd Gerber, E-M. Grischke, Dirk Strumberg, Frederik Marmé, F. Foerster, Andreas Schneeweiss, Peter A. Fasching, C. Windemuth-Kieselbach, A. Mavratzas, S. Baek, S. Hartmann, P. Klare, V. Moebus |
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| Rok vydání: | 2018 |
| Předmět: |
Oncology
Sorafenib Adult medicine.medical_specialty Receptor ErbB-2 medicine.medical_treatment Phases of clinical research Angiogenesis Inhibitors Breast Neoplasms Docetaxel urologic and male genital diseases Placebo Drug Administration Schedule 03 medical and health sciences 0302 clinical medicine Double-Blind Method Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans 030212 general & internal medicine Progression-free survival neoplasms Aged Aged 80 and over Chemotherapy Taxane business.industry General Medicine Middle Aged medicine.disease Metastatic breast cancer Progression-Free Survival Treatment Outcome 030220 oncology & carcinogenesis Surgery Female business medicine.drug |
| Zdroj: | Breast (Edinburgh, Scotland). 45 |
| ISSN: | 1532-3080 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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