TY - JOUR
T1 - Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer
T2 - Results From the randomized phase III adjuvant lapatinib and/or trastuzumab treatment optimization trial
AU - Piccart-Gebhart, Martine
AU - Holmes, Eileen
AU - Baselga, Jośe
AU - De Azambuja, Evandro
AU - Dueck, Amylou C.
AU - Viale, Giuseppe
AU - Zujewski, Jo Anne
AU - Goldhirsch, Aron
AU - Armour, Alison
AU - Pritchard, Kathleen I.
AU - McCullough, Ann E.
AU - Dolci, Stella
AU - McFadden, Eleanor
AU - Holmes, Andrew P.
AU - Tonghua, Liu
AU - Eidtmann, Holger
AU - Dinh, Phuong
AU - Di Cosimo, Serena
AU - Harbeck, Nadia
AU - Tjulandin, Sergei
AU - Im, Young Hyuck
AU - Huang, Chiun Sheng
AU - Díeras, Veronique
AU - Hillman, David W.
AU - Wolff, Antonio C.
AU - Jackisch, Christian
AU - Lang, Istvan
AU - Untch, Michael
AU - Smith, Ian
AU - Boyle, Frances
AU - Xu, Binghe
AU - Gomez, Henry
AU - Suter, Thomas
AU - Gelber, Richard D.
AU - Perez, Edith A.
N1 - Funding Information:
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.
Publisher Copyright:
©2015 by American Society of Clinical Oncology.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2015.62.1797
DO - 10.1200/JCO.2015.62.1797
M3 - Article
C2 - 26598744
AN - SCOPUS:84963612956
SN - 0732-183X
VL - 34
SP - 1034
EP - 1042
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 10
ER -