Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: NSABP protocol B-41.

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Citation: Journal of Clinical Oncology. 30(18_suppl):LBA506, 2012 Jun 20PMID: 28140818Institution: Washington Cancer InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: IN PROCESS -- NOT YET INDEXEDYear: 2012Local holdings: Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008ISSN:
  • 0732-183X
Name of journal: Journal of clinical oncology : official journal of the American Society of Clinical OncologyAbstract: 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/m<sup>2</sup>) 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).All authors: Atkins JN, Azar CA, Baez-Diaz L, Bandos H, Bear HD, Brufsky A, Costantino JP, Farrar WB, Fehrenbacher L, Geyer CE, Kuebler JP, Mamounas EP, Margolese RG, Paik S, Rastogi P, Shibata HR, Swain SM, Tang G, Wolmark NFiscal year: FY2012Digital Object Identifier: Date added to catalog: 2017-08-23
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 28140818 Available 28140818

Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008

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/m<sup>2</sup>) 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).

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