Abstract | BACKGROUND: METHODS: Patients were randomised to paclitaxel (90mg/m(2), weekly, intravenously, 3 weeks on/1 week off) plus sorafenib (400mg, orally, twice daily) or placebo. The primary endpoint was progression-free survival (PFS). A sample size of 220 patients was planned with relative risk ≤ 0.82 (1-sided α=0.14) after 120 events supporting a treatment effect. FINDINGS: Patients were randomised in India (n=170), the United States (n=52) and Brazil (n=15). Median PFS was 6.9 months for sorafenib versus 5.6 months for placebo (hazard ratio (HR)=0.788; 95% confidence interval (CI), 0.558-1.112; P=0.1715 [1-sided P=0.0857]). The addition of sorafenib increased time to progression (median, 8.1 versus 5.6 months; HR=0.674; 95% CI 0.465-0.975; P=0.0343) and improved overall response (67% versus 54%; P=0.0468). Overall survival did not statistically differ (median, 16.8 versus 17.4 months; HR=1.022; 95% CI 0.715-1.461; P=0.904). Grade 3/4 toxicities ( sorafenib versus placebo) included hand-foot skin reaction (31% versus 3%), neutropenia (13% versus 7%) and anaemia (11% versus 6%). Two treatment-related deaths occurred ( malaria and liver dysfunction) in the sorafenib arm. INTERPRETATION: The addition of sorafenib to paclitaxel improved disease control but did not significantly improve PFS to support a phase 3 trial of similar design. Toxicity of the combination was manageable with dose reductions.
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Authors | William J Gradishar, Virginia Kaklamani, Tarini P Sahoo, Dasappa Lokanatha, Vinod Raina, Shailesh Bondarde, Minish Jain, Sunhee Kwon Ro, Nathalie A Lokker, Lee Schwartzberg |
Journal | European journal of cancer (Oxford, England : 1990)
(Eur J Cancer)
Vol. 49
Issue 2
Pg. 312-22
(Jan 2013)
ISSN: 1879-0852 [Electronic] England |
PMID | 22954665
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Ltd. All rights reserved. |
Chemical References |
- Phenylurea Compounds
- Niacinamide
- Sorafenib
- Receptor, ErbB-2
- Paclitaxel
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Topics |
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Breast Neoplasms
(drug therapy, enzymology, pathology)
- Disease-Free Survival
- Double-Blind Method
- Female
- Humans
- Middle Aged
- Neoplasm Metastasis
- Neoplasm Recurrence, Local
(drug therapy, enzymology, pathology)
- Niacinamide
(administration & dosage, adverse effects, analogs & derivatives)
- Paclitaxel
(administration & dosage, adverse effects)
- Phenylurea Compounds
(administration & dosage, adverse effects)
- Receptor, ErbB-2
(metabolism, therapeutic use)
- Sorafenib
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