TY - BOOK AU - Swain, Sandra M TI - Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: NSABP protocol B-41 SN - 0732-183X PY - 2012/// KW - IN PROCESS -- NOT YET INDEXED KW - Washington Cancer Institute KW - Journal Article N1 - Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008 N2 - CONCLUSIONS: Substitution of lapatinib for trastuzumab in combination with the chemotherapy program employed in this study resulted in similar high percentages of pCR in both HR+ and HR- cohorts. Combined HER2-targeted therapy produced a numerically higher pCR percentage than single agent HER2-directed therapy, but the difference was not statistically significant. Central review of HER2 and ER is being conducted to determine if subsets benefiting from the combined HER2-targeted therapy can be identified; FUNDING: GlaxoSmithKline; LBA506 Background: The purposes of this trial are to determine the effect of substituting lapatinib (L) for trastuzumab (T) in combination with weekly paclitaxel (WP) following AC as well as adding L to T with WP following AC on pathologic complete response (pCR) rates; METHODS: Women with HER2-positive operable breast cancer received standard AC q3wks x 4 cycles followed by WP (80 mg/m2) on days 1, 8, and 15 q28 days x 4 cycles. Concurrently with WP, patients received either T (4 mg/kg load, then 2 mg/kg) weekly until surgery, L (1250 mg) daily until surgery, or weekly T plus L (750 mg) daily until surgery. Following surgery, patients received trastuzumab to complete 52 wks of HER2-targeted therapy. The primary endpoint is pCR breast. For each of the two primary comparisons, the Fisher's exact test was used to test the equality of pCR rates. A Hochberg-type step-up procedure was applied to address multiple testings and to control the family-wise error rate at 0.05; RESULTS: 51% were clinically node positive and 63% had HR+ tumors. pCR assessments were available from 519 of 529 patients. pCR percentage was 52.5% for AC->WP+T, 53.2% (p=0.9) for AC->WP+L, and 62% (p=0.075) for AC->WP+TL. pCR percentages in the HR+ subset were 46.7%, 48% (p=0.85), and 55.6% (p=0.18), respectively, and were 65.5%, 60.6% (p=0.57), and 73% (p=0.37) in the HR- cohort. The corresponding pCR breast and nodes percentages were 49.1%, 47.4% (p=0.74), and 60.4% (p=0.04). Grade 3/4 toxicities include diarrhea in 2%, 20%, 27% (p<0.001), and symptomatic Gr 3/4 left ventricular systolic dysfunction in 4%, 4%, and 2% (p=0.49) UR - https://dx.doi.org/10.1200/jco.2012.30.18_suppl.lba506 ER -