TY - JOUR
T1 - Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer
T2 - Final survival analysis of a phase III randomized trial
AU - Cameron, David
AU - Casey, Michelle
AU - Oliva, Cristina
AU - Newstat, Beth
AU - Imwalle, Bradley
AU - Geyer, Charles E.
PY - 2010
Y1 - 2010
N2 - 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/m2) or capecitabine monotherapy (2,500 mg/m2) 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 onotherapy 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.
AB - 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/m2) or capecitabine monotherapy (2,500 mg/m2) 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 onotherapy 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.
KW - Breast cancer
KW - Capecitabine
KW - HER-2
KW - Lapatinib
KW - Metastatic
KW - Survival
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UR - http://www.scopus.com/inward/citedby.url?scp=77957771125&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2009-0181
DO - 10.1634/theoncologist.2009-0181
M3 - Article
C2 - 20736298
AN - SCOPUS:77957771125
VL - 15
SP - 924
EP - 934
JO - Oncologist
JF - Oncologist
SN - 1083-7159
IS - 9
ER -