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Clinical Trial| Volume 148, P287-296, May 2021

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

Published:March 22, 2021DOI:https://doi.org/10.1016/j.ejca.2021.01.053

      Highlights

      • First phase III study of adjuvant dual HER2 blockade for HER2+ breast cancer.
      • 8381 patients with stage I-III HER2+ breast cancer, followed for at least 5 years.
      • Compared chemotherapy + trastuzumab versus chemotherapy + 3 lapatinib-containing arms.
      • Lapatinib associated with increased non-cardiac.
      • Chemotherapy + lapatinib/trastuzumab not superior to chemotherapy + trastuzumab.

      Abstract

      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.

      Keywords

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