Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D)

Alvaro Moreno-Aspitia (Lead / Corresponding author), Eileen M. Holmes, Christian Jackisch, Evandro de Azambuja, Frances Boyle, David W. Hillman, Larissa Korde, Debora Fumagalli, Miguel A. Izquierdo, Ann E. McCullough, Antonio C. Wolff, Kathleen I. Pritchard, Michael Untch, Sébastien Guillaume, Michael S. Ewer, Zhimin Shao, Sung Hoon Sim, Zeba Aziz, Georgia Demetriou, Ajay O. MehtaMichael Andersson, Masakazu Toi, Istvan Lang, Binghe Xu, Ian E. Smith, Carlos H. Barrios, Jose Baselga, Richard D. Gelber, Martine Piccart-Gebhart, ALTTO Steering Committee and Investigators, Florentine Hilbers, Sarra El-Abed, Vasiliki Balta, Celine Schurmans, Daniela D. Rosa, Kamal Saini, Otto Metzger Filho, Robin McConnell, Vicki Paterson, Christine Campbell, Eleanor McFadden, Emma Paterson, Garrick Kassab

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Aim: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial.

Patients and methods: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, nodal status and chemotherapy timing; time to recurrence; overall survival (OS) and safety (overall and cardiac).

Results: At a median follow-up of 6.9 years, 705 DFS events for L+T versus T were observed. Hazard Ratio (HR) for DFS was 0.86 (95% CI, 0.74–1.00) for L+T versus T and 0.93 (95% CI, 0.81–1.08) for T→L versus T. The 6-year DFS were 85%, 84%, and 82% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70–1.06) for L+T versus T and 0.88 (95% CI, 0.71–1.08) for T→L versus T. The 6-year OS were 93%, 92%, and 91% for L+T, T→L, and T, respectively. Subset analyses showed a numerically better HR for DFS in favour of L+T versus T for the hormone-receptor-negative [HR 0.80 (95% CI, 0.64–1.00; 6-yr DFS% = 84% versus 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69–1.00; 6-yr DFS% = 83% versus79%)] subgroups.

Conclusion: T+L did not significantly improve DFS and OS over T alone, both with chemotherapy, and, therefore, cannot be recommended for adjuvant treatment of early-stage HER2-positive breast cancer.

Trial Registration: clinicaltrials.gov Identifier NCT00490139.

Original languageEnglish
Pages (from-to)287-296
Number of pages10
JournalEuropean Journal of Cancer
Early online date22 Mar 2021
Publication statusPublished - May 2021


  • Adjuvant chemotherapy
  • Early breast cancer
  • HER2
  • Lapatinib
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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