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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=84963612956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963612956&partnerID=8YFLogxK
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 -