BIG 2-06 / N063D EGF 106708 / ALTTO BIG 02-06 / N063D (ALTTO) ADJUVANT LAPATINIB AND/ OR TRASTUZUMABClinicalTrials.gov Identifier:
Breast International Group
Frontier Science Scotland
To compare disease-free survival in women with HER-2 over-expressing and/or amplified breast cancer randomised to lapatinib alone versus trastuzumab alone versus trastuzumab followed by lapatinib alone versus lapatinib in combination with trastuzumab.
ALTTO is a global collaboration between BIG-affiliated research groups, the Alliance and other academic research groups. This trial is investigating whether lapatinib, an oral drug, can be as efficient as, or can improve the benefit of, adjuvant trastuzumab.
The trial encompasses a substantial translational component, with central pathology review of the tumour tissue of all patients before randomisation to ensure that the right population is selected for treatment. Additionally, circulating tumour cell and proteomics research will be conducted with some patients to help better understand which patients will likely benefit most from these anti-HER-2 therapies in the future.
This trial has two pragmatic designs, which will broaden its application to actual clinical practice:
- Design 1: anti-HER-2 drugs are given after the completion of anthracycline-based chemotherapy
- Design 2 and 2B: anti-HER-2 drugs are given concomitantly with chemotherapy (taxanes in Design 2) or a non-anthracycline regimen (docetaxel plus carboplatin in Design 2B).
The trial enrolled a total of 8,381 patients, in the period from June 2007 until July 2011. A total of 945 sites in 44 countries participated in the trial.
The first results of this trial were presented at the plenary session of the 2014 ASCO meeting. At a median follow-up of 4.5 years, the number of events was lower than expected. The main analysis indicated a 16% reduction in the risk of a DFS event with the combination of trastzuuamb and lapatinib compared with trastuzumab alone (Hazard ratio: 0.84, 97% CI: 0.70 - 1.02, p=0.048). However, this did not cross the boundary of statistical significance based on the predefined statistical plan (set at p <= 0.025). Currently, extensive biomarker research coordinated by the TransALTTO committee is ongoing to try to determine which subgroups could benefit most of this combination strategy
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