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 Academic Article uri icon

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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.

authors

  • Piccart-Gebhart, Martine
  • Holmes, Eileen
  • Baselga, José
  • de Azambuja, Evandro
  • Dueck, Amylou C
  • Viale, Giuseppe
  • Zujewski, Jo Anne
  • Goldhirsch, Aron
  • Armour, Alison
  • Pritchard, Kathleen
  • McCullough, Ann E
  • Dolci, Stella
  • McFadden, Eleanor
  • Holmes, Andrew P
  • Tonghua, Liu
  • Eidtmann, Holger
  • Dinh, Phuong
  • Di Cosimo, Serena
  • Harbeck, Nadia
  • Tjulandin, Sergei
  • Im, Young-Hyuck
  • Huang, Chiun-Sheng
  • Diéras, Véronique
  • Hillman, David W
  • Wolff, Antonio C
  • Jackisch, Christian
  • Lang, Istvan
  • Untch, Michael
  • Smith, Ian
  • Boyle, Frances
  • Xu, Binghe
  • Gomez, Henry
  • Suter, Thomas
  • Gelber, Richard D
  • Perez, Edith A

publication date

  • April 2016

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