Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab Journal Article

  

Authors:	Schwartzberg, L. S.; Tauer, K. W.; Hermann, R. C.; Makari-Judson, G.; Isaacs, C.; Beck, J. T.; Kaklamani, V.; Stepanski, E. J.; Rugo, H. S.; Wang, W.; Bell-Mcguinn, K.; Kirshner, J. J.; Eisenberg, P.; Emanuelson, R.; Keaton, M.; Levine, E.; Medgyesy, D. C.; Qamar, R.; Starr, A.; Ro, S. K.; Lokker, N. A.; Hudis, C. A.
Article Title:	Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab
Abstract:	Purpose: We assessed adding the multikinase inhibitor sorafenib to gemcitabine or capecitabine in patients with advanced breast cancer whose disease progressed during/after bevacizumab. Experimental Design: This double-blind, randomized, placebo-controlled phase IIb study (ClinicalTrials.gov NCT00493636) enrolled patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer and prior bevacizumab treatment. Patients were randomized to chemotherapy with sorafenib (400 mg, twice daily) or matching placebo. Initially, chemotherapy was gemcitabine (1,000 mg/m2 i.v., days 1, 8/21), but later, capecitabine (1,000 mg/m2 orally twice daily, days 1-14/21) was allowed as an alternative. The primary endpoint was progression-free survival (PFS). Results: One hundred and sixty patients were randomized. More patients received gemcitabine (82.5%) than capecitabine (17.5%). Sorafenib plus gemcitabine/capecitabine was associated with a statistically significant prolongation in PFS versus placebo plus gemcitabine/capecitabine [3.4 vs. 2.7 months; HR = 0.65; 95% confidence interval (CI): 0.45-0.95; P = 0.02], time to progression was increased (median, 3.6 vs. 2.7 months; HR = 0.64; 95% CI: 0.44-0.93; P = 0.02), and overall response rate was 19.8% versus 12.7% (P = 0.23). Median survival was 13.4 versus 11.4 months for sorafenib versus placebo (HR = 1.01; 95% CI: 0.71-1.44; P = 0.95). Addition of sorafenib versus placebo increased grade 3/4 hand-foot skin reaction (39% vs. 5%), stomatitis (10% vs. 0%), fatigue (18% vs. 9%), and dose reductions that were more frequent (51.9% vs. 7.8%). Conclusion: The addition of sorafenib to gemcitabine/capecitabine provided a clinically small but statistically significant PFS benefit in HER2-negative advanced breast cancer patients whose disease progressed during/after bevacizumab. Combination treatment was associated with manageable toxicities but frequently required dose reductions. © 2013 AACR.
Keywords:	adult; cancer survival; controlled study; treatment outcome; major clinical study; constipation; fatigue; neutropenia; sorafenib; bevacizumab; placebo; cancer growth; diarrhea; drug dose reduction; drug efficacy; drug safety; hypertension; side effect; treatment duration; capecitabine; gemcitabine; cancer patient; cancer radiotherapy; anorexia; drug eruption; pain; breast cancer; anemia; mucosa inflammation; nausea; randomized controlled trial; stomatitis; thrombocytopenia; vomiting; epidermal growth factor receptor 2; weight reduction; abdominal pain; arthralgia; backache; coughing; drug fever; dyspnea; drug induced headache; hormonal therapy; taxane derivative; anthracycline; double blind procedure; hand foot syndrome; epistaxis
Journal Title:	Clinical Cancer Research
Volume:	19
Issue:	10
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2013-05-15
Start Page:	2745
End Page:	2754
Language:	English
DOI:	10.1158/1078-0432.ccr-12-3177
PROVIDER:	scopus
PUBMED:	23444220
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84878059586&partnerID=40&md5=5ceeb6406450e1b56723c9c8899680bf
Notes:	--- - "Export Date: 1 July 2013" - "CODEN: CCREF" - "Source: Scopus"

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