Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Institut Jules Bordet, Service d'oncologie médicale, Brussels.
Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Institut Jules Bordet, Brussels, Belgium.
ESMO Open. 2024 Nov;9(11):103938. doi: 10.1016/j.esmoop.2024.103938. Epub 2024 Oct 17.
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.
双重抗人表皮生长因子受体 2（HER2）阻断已改善了早期和转移性 HER2 阳性乳腺癌患者的结局。在此，我们报告 ALTTO 试验的最终 10 年分析结果。
ALTTO 试验（NCT00490139）是一项前瞻性、随机、III 期、开放标签、多中心研究，旨在研究辅助化疗和曲妥珠单抗单药、联合或序贯应用拉帕替尼的作用。主要终点是无病生存期（DFS），次要终点包括总生存期（OS）、远处复发时间和安全性。
共有 6281 例 HER2 阳性早期乳腺癌患者纳入最终疗效分析的三组治疗中：曲妥珠单抗（T）、拉帕替尼+曲妥珠单抗（L+T）和曲妥珠单抗序贯拉帕替尼（T→L）。各组间基线特征均衡。中位随访 9.8 年后，拉帕替尼联合曲妥珠单抗和化疗并未显著改善 DFS 或 OS。T、L+T 和 T→L 组的 10 年 DFS 分别为 77%、79%和 79%，10 年 OS 分别为 87%、89%和 89%。三组治疗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，与单独使用曲妥珠单抗相比，使用拉帕替尼+曲妥珠单抗进行双重抗 HER2 阻断治疗并未观察到 DFS 的显著改善。联合组的 10 年生存率与其他探索双重抗 HER2 治疗的研究一致。
