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Clinical Trial
. 2021 May:148:287-296.
doi: 10.1016/j.ejca.2021.01.053. Epub 2021 Mar 23.

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

Alvaro Moreno-Aspitia  1 , Eileen M Holmes  2 , Christian Jackisch  3 , Evandro de Azambuja  4 , Frances Boyle  5 , David W Hillman  6 , Larissa Korde  7 , Debora Fumagalli  8 , Miguel A Izquierdo  9 , Ann E McCullough  10 , Antonio C Wolff  11 , Kathleen I Pritchard  12 , Michael Untch  13 , Sébastien Guillaume  4 , Michael S Ewer  14 , Zhimin Shao  15 , Sung Hoon Sim  16 , Zeba Aziz  17 , Georgia Demetriou  18 , Ajay O Mehta  19 , Michael Andersson  20 , Masakazu Toi  21 , Istvan Lang  22 , Binghe Xu  23 , Ian E Smith  24 , Carlos H Barrios  25 , Jose Baselga  26 , Richard D Gelber  27 , Martine Piccart-Gebhart  4 ; ALTTO Steering Committee and Investigators
Collaborators, Affiliations
Clinical Trial

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

Alvaro Moreno-Aspitia et al. Eur J Cancer. 2021 May.

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: Adjuvant chemotherapy; Early breast cancer; HER2; Lapatinib; Trastuzumab.

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Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships that may be considered as potential competing interests:

Figures

Figure 1.
Figure 1.
ALTTO Study Design. ALTTO indicates Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization; MFU (median follow up); *R, registration.
Figure 2.
Figure 2.
CONSORT Chart. DFS indicates disease-free survival; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC, immunohistochemistry; L, lapatinib; LVEF, left ventricular ejection fraction; T, trastuzumab.
Figure 3.
Figure 3.
3A. DISEASE-FREE SURVIVAL (DFS) ANALYSIS; 3B. OVERALL SURVIVAL (OS) ANALYSIS Kaplan-Meier curves. *p-values are descriptive, not inferential. DFS indicates disease-free survival; Lap, lapatinib; OS, overall survival; and Tras, trastuzumab.
See this image and copyright information in PMC

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