Piccart-Gebhart, M., Holmes, E., Baselga, J., de Azambuja, E., Dueck, A. C., Viale, G., Zujewski, J. A., Goldhirsch, A., Armour, A., Pritchard, K. I., McCullough, A. E., Dolci, S., McFadden, E., Holmes, A. P., Liu, T. H., Eidtmann, H., Dinh, P., Di Cosimo, S., Harbeck, N., Tjulandin, S., Im, Y. H., Huang, C. S., Dieras, V., Hillman, D. W., Wolff, A. C., Jackisch, C., Lang, I., Untch, M., Smith, I., Boyle, F., Xu, B. H., Gomez, H., Suter, T., Gelber, R. D., Perez, E. A. (2016) Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial. JOURNAL OF CLINICAL ONCOLOGY, 34 (10). pp. 1034-1042. ISSN 0732-183X

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Abstract

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2-positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2-positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T. L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P <= .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T. L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care.

Item Type:	Article
Authors (ICR Faculty only):	Smith, Ian
All Authors:	Piccart-Gebhart, M., Holmes, E., Baselga, J., de Azambuja, E., Dueck, A. C., Viale, G., Zujewski, J. A., Goldhirsch, A., Armour, A., Pritchard, K. I., McCullough, A. E., Dolci, S., McFadden, E., Holmes, A. P., Liu, T. H., Eidtmann, H., Dinh, P., Di Cosimo, S., Harbeck, N., Tjulandin, S., Im, Y. H., Huang, C. S., Dieras, V., Hillman, D. W., Wolff, A. C., Jackisch, C., Lang, I., Untch, M., Smith, I., Boyle, F., Xu, B. H., Gomez, H., Suter, T., Gelber, R. D., Perez, E. A.
Additional Information:	ISI Document Delivery No.: DJ6PA Times Cited: 1 Cited Reference Count: 33 Piccart-Gebhart, Martine Holmes, Eileen Baselga, Jose de Azambuja, Evandro Dueck, Amylou C. Viale, Giuseppe Zujewski, Jo Anne Goldhirsch, Aron Armour, Alison Pritchard, Kathleen I. McCullough, Ann E. Dolci, Stella McFadden, Eleanor Holmes, Andrew P. Liu Tonghua Eidtmann, Holger Phuong Dinh Di Cosimo, Serena Harbeck, Nadia Tjulandin, Sergei Im, Young-Hyuck Huang, Chiun-Sheng Dieras, Veronique Hillman, David W. Wolff, Antonio C. Jackisch, Christian Lang, Istvan Untch, Michael Smith, Ian Boyle, Frances Xu, Binghe Gomez, Henry Suter, Thomas Gelber, Richard D. Perez, Edith A. GlaxoSmithKline; National Cancer Institute of the National Institutes of Health [U10CA180821, U10CA180882, CA025224] Supported by GlaxoSmithKline and the National Cancer Institute of the National Institutes of Health under Grant No. U10CA180821 and U10CA180882 to the Alliance for Clinical Trials in Oncology and CA025224 to the legacy North Central Cancer Treatment Group. 1 2 AMER SOC CLINICAL ONCOLOGY ALEXANDRIA J CLIN ONCOL
Uncontrolled Keywords:	OPEN-LABEL PLUS CAPECITABINE CHEMOTHERAPY THERAPY SURVIVAL EFFICACY SAFETY COMBINATION INHIBITOR DOCETAXEL
Research teams:	Clinical Units > Breast Unit
Depositing User:	Barry Jenkins
Date Deposited:	26 May 2016 14:52
Last Modified:	26 May 2016 14:52
URI:	http://publications.icr.ac.uk/id/eprint/15025

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