par Piccart-Gebhart, Martine ;Pritchard, Kathleen;McCullough, Ann A.E.;Dolci, Stella;McFadden, Eleanor;Holmes, Andrew A.P.;Tonghua, Liu;Eidtmann, Holger;Dinh, Phuong ;Di Cosimo, Serena;Harbeck, Nadia;Holmes, Eileen;Tjulandin, Sergei;Im, Young Hyuck;Huang, Chiun Sheng;Diéras, Véronique;Hillman, David D.W.;Wolff, Antonio C;Jackisch, Christian;Lang, Istvan;Untch, Michael;Smith, Ian;Baselga, José;Boyle, Frances;Xu, Binghe;Gomez, Henry;Suter, Thomas;Gelber, Richard R.D.;Perez, Edith A;de Azambuja, Evandro ;Dueck, Amylou A.C.;Viale, Giuseppe;Zujewski, Jo Anne;Goldhirsch, Aron;Armour, Alison
Référence Journal of clinical oncology, 34, 10, page (1034-1042)
Publication Publié, 2016-04
Référence Journal of clinical oncology, 34, 10, page (1034-1042)
Publication Publié, 2016-04
Article révisé par les pairs
Résumé : | 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. |