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 Article


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.; Tonghua, L.; Eidtmann, H.; Dinh, P.; Di Cosimo, S.; Harbeck, N.; Tjulandin, S.; Im, Y. H.; Huang, C. S.; Diéras, V.; Hillman, D. W.; Wolff, A. C.; Jackisch, C.; Lang, I.; Untch, M.; Smith, I.; Boyle, F.; Xu, B.; Gomez, H.; Suter, T.; Gelber, R. D.; Perez, E. A.
Article Title: 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
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. ©2015 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 34
Issue: 10
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2016-04-01
Start Page: 1034
End Page: 1042
Language: English
DOI: 10.1200/jco.2015.62.1797
PROVIDER: scopus
PUBMED: 26598744
PMCID: PMC4872016
DOI/URL:
Notes: Article -- Export Date: 2 May 2016 -- Source: Scopus
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MSK Authors
  1. Jose T Baselga
    389 Baselga