RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer
© 2017. Introduction: Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. In this randomized, double-blind, placebo-controlled phase III trial we assessed first- or second-line capecitabine with sorafenib or placebo in patients with locally advanced/metastatic HER2-n...
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| Format: | Journal Article |
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2017
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| Online Access: | http://hdl.handle.net/20.500.11937/58524 |
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| author | Baselga, J. Zamagni, C. Gómez, P. Bermejo, B. Nagai, S. Melichar, B. Chan, Arlene Mángel, L. Bergh, J. Costa, F. Gómez, H. Gradishar, W. Hudis, C. Rapoport, B. Roché, H. Patricia, M. Huang, L. Meinhardt, G. Zhang, J. Schwartzberg, L. |
| author_facet | Baselga, J. Zamagni, C. Gómez, P. Bermejo, B. Nagai, S. Melichar, B. Chan, Arlene Mángel, L. Bergh, J. Costa, F. Gómez, H. Gradishar, W. Hudis, C. Rapoport, B. Roché, H. Patricia, M. Huang, L. Meinhardt, G. Zhang, J. Schwartzberg, L. |
| author_sort | Baselga, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2017. Introduction: Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. In this randomized, double-blind, placebo-controlled phase III trial we assessed first- or second-line capecitabine with sorafenib or placebo in patients with locally advanced/metastatic HER2-negative breast cancer resistant to a taxane and anthracycline and with known estrogen/progesterone receptor status. Patients and Methods: A total of 537 patients were randomized to capecitabine 1000 mg/m 2 orally twice per day for days 1 to 14 every 21 days with oral sorafenib 600 mg/d or placebo. The primary end point was progression-free survival (PFS). Patients were stratified according to hormone receptor status, previous chemotherapies for metastatic breast cancer, and geographic region. Results: Treatment with sorafenib with capecitabine, compared with capecitabine with placebo, did not prolong median PFS (5.5 vs. 5.4 months; hazard ratio [HR], 0.973; 95% confidence interval [CI] , 0.779-1.217; P = .811) or overall survival (OS; 18.9 vs. 20.3 months; HR, 1.195; 95% CI, 0.943-1.513; P = .140); or enhance overall response rate (ORR; 13.5% vs. 15.5%; P = .515). Any grade toxicities (sorafenib vs. placebo) included palmar-plantar erythrodysesthesia syndrome (79.2% vs. 59.6%), diarrhea (47.3% vs. 37.8%), mucosal inflammation (15.4% vs. 6.7%), and hypertension (26.2% vs. 5.6%). Grade 3/4 toxicities included PPES (15.4% vs. 7.1%), diarrhea (4.2% vs. 6.4%), and vomiting (3.5% vs. 0.7%). Conclusion: The combination of sorafenib with capecitabine did not improve PFS, OS, or ORR in patients with HER2-negative advanced breast cancer. Rates of Grade 3 toxicities were higher in the sorafenib arm. |
| first_indexed | 2025-11-14T10:13:17Z |
| format | Journal Article |
| id | curtin-20.500.11937-58524 |
| institution | Curtin University Malaysia |
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| last_indexed | 2025-11-14T10:13:17Z |
| publishDate | 2017 |
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| spelling | curtin-20.500.11937-585242017-11-24T05:46:21Z RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer Baselga, J. Zamagni, C. Gómez, P. Bermejo, B. Nagai, S. Melichar, B. Chan, Arlene Mángel, L. Bergh, J. Costa, F. Gómez, H. Gradishar, W. Hudis, C. Rapoport, B. Roché, H. Patricia, M. Huang, L. Meinhardt, G. Zhang, J. Schwartzberg, L. © 2017. Introduction: Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. In this randomized, double-blind, placebo-controlled phase III trial we assessed first- or second-line capecitabine with sorafenib or placebo in patients with locally advanced/metastatic HER2-negative breast cancer resistant to a taxane and anthracycline and with known estrogen/progesterone receptor status. Patients and Methods: A total of 537 patients were randomized to capecitabine 1000 mg/m 2 orally twice per day for days 1 to 14 every 21 days with oral sorafenib 600 mg/d or placebo. The primary end point was progression-free survival (PFS). Patients were stratified according to hormone receptor status, previous chemotherapies for metastatic breast cancer, and geographic region. Results: Treatment with sorafenib with capecitabine, compared with capecitabine with placebo, did not prolong median PFS (5.5 vs. 5.4 months; hazard ratio [HR], 0.973; 95% confidence interval [CI] , 0.779-1.217; P = .811) or overall survival (OS; 18.9 vs. 20.3 months; HR, 1.195; 95% CI, 0.943-1.513; P = .140); or enhance overall response rate (ORR; 13.5% vs. 15.5%; P = .515). Any grade toxicities (sorafenib vs. placebo) included palmar-plantar erythrodysesthesia syndrome (79.2% vs. 59.6%), diarrhea (47.3% vs. 37.8%), mucosal inflammation (15.4% vs. 6.7%), and hypertension (26.2% vs. 5.6%). Grade 3/4 toxicities included PPES (15.4% vs. 7.1%), diarrhea (4.2% vs. 6.4%), and vomiting (3.5% vs. 0.7%). Conclusion: The combination of sorafenib with capecitabine did not improve PFS, OS, or ORR in patients with HER2-negative advanced breast cancer. Rates of Grade 3 toxicities were higher in the sorafenib arm. 2017 Journal Article http://hdl.handle.net/20.500.11937/58524 10.1016/j.clbc.2017.05.006 restricted |
| spellingShingle | Baselga, J. Zamagni, C. Gómez, P. Bermejo, B. Nagai, S. Melichar, B. Chan, Arlene Mángel, L. Bergh, J. Costa, F. Gómez, H. Gradishar, W. Hudis, C. Rapoport, B. Roché, H. Patricia, M. Huang, L. Meinhardt, G. Zhang, J. Schwartzberg, L. RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer |
| title | RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer |
| title_full | RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer |
| title_fullStr | RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer |
| title_full_unstemmed | RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer |
| title_short | RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer |
| title_sort | resilience: phase iii randomized, double-blind trial comparing sorafenib with capecitabine versus placebo with capecitabine in locally advanced or metastatic her2-negative breast cancer |
| url | http://hdl.handle.net/20.500.11937/58524 |