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

• Published in: Journal of clinical oncology Vol. 30; no. 18_suppl; p. LBA506
• Main Authors: Robidoux, Andre, Tang, Gong, Rastogi, Priya, Geyer, Charles E., Azar, Catherine A., Atkins, James Norman, Fehrenbacher, Louis, Bear, Harry Douglas, Baez-Diaz, Luis, Kuebler, J. Phillip, Margolese, Richard G., Farrar, William Blair, Brufsky, Adam, Shibata, Henry R., Bandos, Hanna, Paik, Soonmyung, Costantino, Joseph P., Swain, Sandra M., Mamounas, Eleftherios P., Wolmark, Norman
• Format: Journal Article
• Language: English
• Published: 20.06.2012
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2012.30.18_suppl.lba506

Abstract only 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 2 ) 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). 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.