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.CHIUN-SHENG HUANGDiéras 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.2020-03-232020-03-2320160732-183Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84963612956&doi=10.1200%2fJCO.2015.62.1797&partnerID=40&md5=f5d59ae82e311182f1e74c010f8c4d63https://scholars.lib.ntu.edu.tw/handle/123456789/477730Background 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.[SDGs]SDG3carboplatin; docetaxel; lapatinib; paclitaxel; trastuzumab; antineoplastic agent; epidermal growth factor receptor 2; ERBB2 protein, human; lapatinib; quinazoline derivative; trastuzumab; tumor marker; adult; aged; Article; breast cancer; cancer adjuvant therapy; cardiotoxicity; clinical protocol; controlled study; diarrhea; disease free survival; drug fatality; drug safety; drug withdrawal; epidermal growth factor receptor 2 positive breast cancer; epidermal growth factor receptor 2 positive breast cancer; febrile neutropenia; female; hepatobiliary disease; human; incidence; interstitial pneumonia; liver toxicity; loading drug dose; major clinical study; multicenter study; multiple cycle treatment; neutropenia; phase 3 clinical trial; priority journal; randomized controlled trial; rash; skin toxicity; treatment outcome; treatment response; adjuvant chemotherapy; Breast Neoplasms; cancer staging; chemistry; clinical trial; drug administration; follow up; Kaplan Meier method; middle aged; pathology; patient selection; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Staging; Patient Selection; Quinazolines; Receptor, ErbB-2; Trastuzumab; Treatment Outcomejournal article10.1200/JCO.2015.62.1797265987442-s2.0-84963612956