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Lapatinib Plus Capecitabine in Women with HER-2–Positive Advanced Breast Cancer: Final Survival Analysis of a Phase III Randomized Trial
OBJECTIVES. A planned interim analysis of study EGF100151 prompted early termination of enrollment based on a longer time to progression with lapatinib and capecitabine than with capecitabine alone in patients with human epidermal growth factor receptor (HER)-2(+) previously treated advanced breast...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AlphaMed Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228041/ https://www.ncbi.nlm.nih.gov/pubmed/20736298 http://dx.doi.org/10.1634/theoncologist.2009-0181 |
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author | Cameron, David Casey, Michelle Oliva, Cristina Newstat, Beth Imwalle, Bradley Geyer, Charles E. |
author_facet | Cameron, David Casey, Michelle Oliva, Cristina Newstat, Beth Imwalle, Bradley Geyer, Charles E. |
author_sort | Cameron, David |
collection | PubMed |
description | OBJECTIVES. A planned interim analysis of study EGF100151 prompted early termination of enrollment based on a longer time to progression with lapatinib and capecitabine than with capecitabine alone in patients with human epidermal growth factor receptor (HER)-2(+) previously treated advanced breast cancer or metastatic breast cancer (MBC). Here, we report final analyses of overall survival. PATIENTS AND METHODS. Women with HER-2(+) MBC who progressed after regimens that included, but were not limited to, anthracyclines, taxanes, and trastuzumab, were randomized to lapatinib (1,250 mg/day) plus capecitabine (2,000 mg/m(2)) or capecitabine monotherapy (2,500 mg/m(2)) on days 1–14 of a 21-day cycle. RESULTS. At enrollment termination, 399 patients were randomized, and nine were being screened and were offered combination treatment. In total, 207 and 201 patients were enrolled to combination therapy and monotherapy, respectively. Thirty-six patients receiving monotherapy crossed over to combination therapy following enrollment termination. The median overall survival times were 75.0 weeks for the combination arm and 64.7 weeks for the monotherapy arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.71–1.08; p = .210). A Cox regression analysis considering crossover as a time-dependent covariate suggested a 20% lower risk for death for patients treated with combination therapy (HR, 0.80; 95% CI, 0.64–0.99; p = .043). The low incidence of serious adverse events was consistent with previously reported rates. CONCLUSIONS. Although premature enrollment termination and subsequent crossover resulted in insufficient power to detect differences in overall survival, exploratory analyses demonstrate a trend toward a survival advantage with lapatinib plus capecitabine. These data continue to support the efficacy of lapatinib in patients with HER-2(+) MBC. |
format | Online Article Text |
id | pubmed-3228041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | AlphaMed Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32280412012-04-25 Lapatinib Plus Capecitabine in Women with HER-2–Positive Advanced Breast Cancer: Final Survival Analysis of a Phase III Randomized Trial Cameron, David Casey, Michelle Oliva, Cristina Newstat, Beth Imwalle, Bradley Geyer, Charles E. Oncologist Academia–Pharma Intersect OBJECTIVES. A planned interim analysis of study EGF100151 prompted early termination of enrollment based on a longer time to progression with lapatinib and capecitabine than with capecitabine alone in patients with human epidermal growth factor receptor (HER)-2(+) previously treated advanced breast cancer or metastatic breast cancer (MBC). Here, we report final analyses of overall survival. PATIENTS AND METHODS. Women with HER-2(+) MBC who progressed after regimens that included, but were not limited to, anthracyclines, taxanes, and trastuzumab, were randomized to lapatinib (1,250 mg/day) plus capecitabine (2,000 mg/m(2)) or capecitabine monotherapy (2,500 mg/m(2)) on days 1–14 of a 21-day cycle. RESULTS. At enrollment termination, 399 patients were randomized, and nine were being screened and were offered combination treatment. In total, 207 and 201 patients were enrolled to combination therapy and monotherapy, respectively. Thirty-six patients receiving monotherapy crossed over to combination therapy following enrollment termination. The median overall survival times were 75.0 weeks for the combination arm and 64.7 weeks for the monotherapy arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.71–1.08; p = .210). A Cox regression analysis considering crossover as a time-dependent covariate suggested a 20% lower risk for death for patients treated with combination therapy (HR, 0.80; 95% CI, 0.64–0.99; p = .043). The low incidence of serious adverse events was consistent with previously reported rates. CONCLUSIONS. Although premature enrollment termination and subsequent crossover resulted in insufficient power to detect differences in overall survival, exploratory analyses demonstrate a trend toward a survival advantage with lapatinib plus capecitabine. These data continue to support the efficacy of lapatinib in patients with HER-2(+) MBC. AlphaMed Press 2010-09 2010-08-24 /pmc/articles/PMC3228041/ /pubmed/20736298 http://dx.doi.org/10.1634/theoncologist.2009-0181 Text en ©AlphaMed Press available online without subscription through the open access option. |
spellingShingle | Academia–Pharma Intersect Cameron, David Casey, Michelle Oliva, Cristina Newstat, Beth Imwalle, Bradley Geyer, Charles E. Lapatinib Plus Capecitabine in Women with HER-2–Positive Advanced Breast Cancer: Final Survival Analysis of a Phase III Randomized Trial |
title | Lapatinib Plus Capecitabine in Women with HER-2–Positive Advanced Breast Cancer: Final Survival Analysis of a Phase III Randomized Trial |
title_full | Lapatinib Plus Capecitabine in Women with HER-2–Positive Advanced Breast Cancer: Final Survival Analysis of a Phase III Randomized Trial |
title_fullStr | Lapatinib Plus Capecitabine in Women with HER-2–Positive Advanced Breast Cancer: Final Survival Analysis of a Phase III Randomized Trial |
title_full_unstemmed | Lapatinib Plus Capecitabine in Women with HER-2–Positive Advanced Breast Cancer: Final Survival Analysis of a Phase III Randomized Trial |
title_short | Lapatinib Plus Capecitabine in Women with HER-2–Positive Advanced Breast Cancer: Final Survival Analysis of a Phase III Randomized Trial |
title_sort | lapatinib plus capecitabine in women with her-2–positive advanced breast cancer: final survival analysis of a phase iii randomized trial |
topic | Academia–Pharma Intersect |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228041/ https://www.ncbi.nlm.nih.gov/pubmed/20736298 http://dx.doi.org/10.1634/theoncologist.2009-0181 |
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