Abstract：
The global phase 3 DESTINY-Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY-Breast03. In total, 309 patients (149 in the T-DXd arm and 160 in the T-DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow-up in the Asian subpopulation was 29.0 months with T-DXd and 26.0 months with T-DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22-0.41) favoring T-DXd over T-DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T-DXd arm and was 37.7 months in the T-DM1 arm. The median treatment duration was 15.4 months with T-DXd and 5.5 months with T-DM1. The incidence of grade ≥3 drug-related treatment-emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY-Breast03 population. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T-DXd and 2.5% treated with T-DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit-risk profile of T-DXd in HER2-positive mBC, including in the Asian subgroup.
摘要：
全球3期DESTINY-Breast03研究（ClinicalTrials.gov;NCT03529110）显示，曲妥珠单抗deruxtecan（T-DXd）在无进展生存期（PFS）和总生存期（OS）方面具有统计学意义和临床意义的改善。患有人表皮生长因子受体2（HER2）阳性的转移性乳腺癌（HER2）患者。这里,我们报告了一项纳入DESTINY-Breast03的亚洲患者的亚组分析.总的来说,来自亚洲国家和地区的309名患者（T-DXd组149名，T-DM1组160名）被随机分组。在数据截止时（2022年7月25日），亚洲亚群的中位随访时间T-DXd为29.0个月,T-DM1为26.0个月.PFS（由盲法独立中央审查确定）的风险比为0.30（95％置信区间0.22-0.41），T-DXd优于T-DM1（PFS中位数25.1与5.4个月）。T-DXd臂未达到中位OS，T-DM1臂为37.7个月。T-DXd的中位治疗时间为15.4个月，T-DM1的中位治疗时间为5.5个月。两个治疗组之间≥3级药物相关治疗引起的不良事件的发生率相似（49.0％vs.46.5％），与整个DESTINY-Breast03人口一致。在接受T-DXd治疗的患者中，12.9％和接受T-DM1治疗的患者中，有2.5％发生了与药物相关的间质性肺病或肺炎，在日本患者中发生率更高；这些事件均为≥4级事件。这些疗效和安全性数据加强了T-DXd在HER2阳性mBC中的有利获益-风险特征，包括亚洲分组。
