TY - JOUR
T1 - A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab
T2 - Updated efficacy and biomarker analyses
AU - Cameron, David
AU - Casey, Michelle
AU - Press, Michael
AU - Lindquist, Deborah
AU - Pienkowski, Tadeusz
AU - Romieu, C. Gilles
AU - Chan, Stephen
AU - Jagiello-Gruszfeld, Agnieszka
AU - Kaufman, Bella
AU - Crown, John
AU - Chan, Arlene
AU - Campone, Mario
AU - Viens, Patrice
AU - Davidson, Neville
AU - Gorbounova, Vera
AU - Raats, Johannes Isaac
AU - Skarlos, Dimosthenis
AU - Newstat, Beth
AU - Roychowdhury, Debasish
AU - Paoletti, Paolo
AU - Oliva, Cristina
AU - Rubin, Stephen
AU - Stein, Steven
AU - Geyer, Charles E.
PY - 2008/12
Y1 - 2008/12
N2 - Purpose: Lapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Updated efficacy and initial biomarker results from this trial are reported. Methods: Women with HER2-positive, locally advanced or metastatic breast cancer previously treated with anthracycline-, taxane-, and trastuzumab-containing regimens were randomized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m2 days 1-14 of a 21-day cycle or capecitabine 2,500 mg/m2 on the same schedule. The primary endpoint was time to progression (TTP) as determined by an independent review panel. Relationship between progression-free survival (PFS) and tumor HER2 expression and serum levels of HER2 extracellular domain (ECD) were assessed. Results: 399 women were randomized. The addition of lapatinib prolonged TTP with a hazard ratio (HR) of 0.57 (95% CI, 0.43-0.77; P < 0.001) and provided a trend toward improved overall survival (HR: 0.78, 95% CI: 0.55-1.12, P = 0.177), and fewer cases with CNS involvement at first progression (4 vs. 13, P = 0.045). Baseline serum HER2 ECD did not predict for benefit from lapatinib. Conclusion: The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive, advanced breast cancer progressing after treatment with anthracycline-, taxane-, and trastuzumab-based therapy. Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine.
AB - Purpose: Lapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Updated efficacy and initial biomarker results from this trial are reported. Methods: Women with HER2-positive, locally advanced or metastatic breast cancer previously treated with anthracycline-, taxane-, and trastuzumab-containing regimens were randomized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m2 days 1-14 of a 21-day cycle or capecitabine 2,500 mg/m2 on the same schedule. The primary endpoint was time to progression (TTP) as determined by an independent review panel. Relationship between progression-free survival (PFS) and tumor HER2 expression and serum levels of HER2 extracellular domain (ECD) were assessed. Results: 399 women were randomized. The addition of lapatinib prolonged TTP with a hazard ratio (HR) of 0.57 (95% CI, 0.43-0.77; P < 0.001) and provided a trend toward improved overall survival (HR: 0.78, 95% CI: 0.55-1.12, P = 0.177), and fewer cases with CNS involvement at first progression (4 vs. 13, P = 0.045). Baseline serum HER2 ECD did not predict for benefit from lapatinib. Conclusion: The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive, advanced breast cancer progressing after treatment with anthracycline-, taxane-, and trastuzumab-based therapy. Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine.
KW - Advanced breast cancer
KW - Biomarker
KW - Capecitabine
KW - Dual tyrosine kinase inhibitor
KW - HER2-positive
KW - Lapatinib
KW - Metastatic breast cancer
KW - Phase III
UR - http://www.scopus.com/inward/record.url?scp=56549113680&partnerID=8YFLogxK
U2 - 10.1007/s10549-007-9885-0
DO - 10.1007/s10549-007-9885-0
M3 - Article
C2 - 18188694
AN - SCOPUS:56549113680
SN - 0167-6806
VL - 112
SP - 533
EP - 543
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -