ALTTO试验终期分析：HER2阳性早期乳腺癌患者辅助性曲妥珠单抗与拉帕替尼的序贯或联合方案【BIG 2-06/NCCTG N063D（联盟）】

Final analysis of the ALTTO trial: adjuvant trastuzumab in sequence or in combination with lapatinib in patients with HER2-positive early breast cancer [BIG 2-06/NCCTG N063D (Alliance)]

ESMO Open

影响因子:8.3

分区:医学1区 Top / 肿瘤学2区

发表日期:2024 Nov

作者: E de Azambuja, M Piccart-Gebhart, S Fielding, J Townend, D W Hillman, M Colleoni, R Roylance, C M Kelly, J Lombard, S El-Abed, A Choudhury, L Korde, M Vicente, S Chumsri, R Rodeheffer, S L Ellard, A C Wolff, J Holtschmidt, I Lang, M Untch, F Boyle, B Xu, G Werutsky, J Tujakowski, C-S Huang, N B Baruch, J Bliss, A Ferro, J Gralow, S-B Kim, J R Kroep, I Krop, S Kuemmel, R McConnell, L Moscetti, A S Knop, F van Duijnhoven, H Gomez, D Cameron, S Di Cosimo, R D Gelber, A Moreno-Aspitia

DOI: 10.1016/j.esmoop.2024.103938

摘要

双重抗人表皮生长因子受体2（HER2）封锁已改善早期和转移性HER2阳性乳腺癌患者的预后。本文呈现ALTTO试验的10年终期分析。ALTTO试验（NCT00490139）是一项前瞻性随机、多中心III期开放标签研究，探讨辅助化疗和单用曲妥珠单抗，以及联合或序贯拉帕替尼的作用。主要终点为无疾病生存期（DFS），次要终点包括总生存期（OS）、远处复发时间和安全性。最终分析纳入6281例HER2阳性早期乳腺癌患者，分为三组：曲妥珠单抗（T）、拉帕替尼+曲妥珠单抗（L+T）和曲妥珠单抗后接拉帕替尼（T→L）。各组基线特征均衡。在中位随访9.8年时，添加拉帕替尼至曲妥珠单抗和化疗未显著改善DFS或OS。10年DFS分别为77%（T组）、79%（L+T）和79%（T→L），10年OS分别为87%、89%和89%。三组的任何心脏事件发生率均较低且相似。随着随访时间的延长，双重抗HER2封锁（拉帕替尼+曲妥珠单抗）组的DFS没有显著改善，相较于单用曲妥珠单抗。组合治疗组的10年生存率与其他研究探索双抗HER2治疗的结果一致。

Abstract

Dual anti-human epidermal growth factor receptor 2 (HER2) blockade has improved the outcomes of patients with early and metastatic HER2-positive breast cancer. Here we present the final 10-year analysis of the ALTTO trial.The ALTTO trial (NCT00490139) is a prospective randomized, phase III, open-label, multicenter study that investigated the role of adjuvant chemotherapy and trastuzumab alone, in combination or sequentially with lapatinib. The primary endpoint was disease-free survival (DFS) and secondary endpoints included overall survival (OS), time to distant recurrence and safety.Overall, 6281 patients with HER2-positive early breast cancer were included in the final efficacy analysis in three treatment groups: trastuzumab (T), lapatinib + trastuzumab (L + T) and trastuzumab followed by lapatinib (T→L). Baseline characteristics were well balanced between groups. At a median follow-up of 9.8 years, the addition of lapatinib to trastuzumab and chemotherapy did not significantly improve DFS nor OS. The 10-year DFS was 77% in T, 79% in L + T and 79% in T→L, and the 10-year OS was 87%, 89% and 89%, respectively. The incidence of any cardiac event was low and similar in the three treatment groups.With a longer follow-up, no significant improvement was observed in DFS in patients treated with dual anti-HER2 blockade with lapatinib + trastuzumab compared to trastuzumab alone. The 10-year survival rates for the combination group are consistent with other studies that have explored dual anti-HER2 therapy.