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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

1 avr. 2016Journal of Clinical Oncology

DOI : 10.1200/jco.2015.62.1797

Auteurs

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

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.