背景:脑转移(BM)是HER2阳性转移性乳腺癌(BC)的破坏性并发症,迫切需要提供优化的局部和全身疾病控制的治疗策略。抗体-药物缀合物(ADC)曲妥珠单抗deruxtecan(T-DXd)比曲妥珠单抗emtansine改善了无进展生存期(PFS)和总生存期(OS),但有关颅内活动的数据有限。在TUXEDO-1的主要结果分析中,据报道T-DXd具有较高的颅内反应率(RR)。这里,我们报告最终的PFS和OS结果。
方法:TUXEDO-1使患有HER2阳性BC和活动性BM(新诊断或进展)的成年患者没有立即进行局部治疗的指征。主要终点是颅内RR;次要终点包括PFS,操作系统,安全,生活质量(QoL),和神经认知功能。使用Kaplan-Meier方法估计PFS和OS,并在符合方案的人群中进行分析。
结果:中位随访26.5个月时,中位PFS为21个月(95%CI13.3-n.r.),未达到中位OS(95%CI22.2-n.r.).随着随访时间的延长,未观察到新的安全性信号.最常见的3级不良事件是疲劳(20%)。在每位患者中观察到2级间质性肺病和3级症状性左心室射血分数下降。QoL在治疗期间保持。
结论:T-DXd在活动性HER2阳性BCBM患者中产生了延长的颅内和外疾病控制,与关键试验的结果一致。这些结果支持ADC作为活动性BM的全身疗法的概念。
BACKGROUND: Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report final PFS and OS results.
METHODS: TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population.
RESULTS: At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period.
CONCLUSIONS: T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of ADCs as systemic therapy for active BM.