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.
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 / M. Piccart-Gebhart, E. Holmes, J. Baselga, E. de Azambuja, A.C. Dueck, G. Viale, J.A. Zujewski, A. Goldhirsch, A. Armour, K.I. Pritchard, A.E. Mccullough, S. Dolci, E. Mcfadden, A.P. Holmes, L. Tonghua, H. Eidtmann, P. Dinh, S. Di Cosimo, N. Harbeck, S. Tjulandin, Y. Im, C. Huang, V. Diéras, D.W. Hillman, A.C. Wolff, C. Jackisch, I. Lang, M. Untch, I. Smith, F. Boyle, B. Xu, H. Gomez, T. Suter, R.D. Gelber, E.A. Perez. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 34:10(2016 Apr 01), pp. 1034-1042.
|Titolo:||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|
|Settore Scientifico Disciplinare:||Settore MED/08 - Anatomia Patologica|
|Data di pubblicazione:||1-apr-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1200/JCO.2015.62.1797|
|Appare nelle tipologie:||01 - Articolo su periodico|