Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial.

patients_and_methods

In the randomised, open-label, phase III TROPION-Breast02 trial, patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option were randomly assigned 1:1 to datopotamab deruxtecan (Dato-DXd; 6 mg/kg intravenously every 3 weeks) or investigator's choice of chemotherapy.

在随机、开放标签、III期TROPION-Breast02试验中，对于那些免疫治疗不是选项的先前未经治疗、局部复发无法手术或转移性TNBC患者，按1:1的比例随机分配接受datopotamab deruxtecan（Dato-DXd；每3周静脉注射6 mg/kg）或研究者选择的化疗方案。

Randomisation was stratified by geographic location, disease-free interval, and programmed cell death ligand-1 status.

随机分组根据地理位置、无病间隔期和程序性细胞死亡配体-1状态进行了分层。

Dual primary endpoints were progression-free survival(PFS; blinded independent central review per RECIST version 1.1) and overall survival(OS).

双重主要终点是无进展生存期（PFS；根据RECIST版本1.1进行的盲法独立中央审查）和总生存期（OS）。

Efficacy analyses were performed in the intention-to-treatpopulation.

疗效分析在意向治疗人群中进行。

Safety analyses included all patients who received ≥1 dose of study treatment.

安全性分析包括所有接受≥1剂研究治疗的患者。

Results

Between 16 May 2022 and 11 June 2024, 644 patients were randomly assigned to receive Dato-DXd (n = 323) or chemotherapy (n = 321).

在2022年5月16日至2024年6月11日期间，644名患者被随机分配接受Dato-DXd治疗（n = 323）或化疗（n = 321）。

Median PFS was 10.8 months [95% confidence interval(CI) 8.6-13.0] with Dato-DXd and 5.6 months (95% CI 5.0-7.0) with chemotherapy [hazard ratio0.57 (99% CI 0.44-0.73); P < 0.0001].

Dato-DXd治疗组的中位无进展生存期（PFS）为10.8个月（95%置信区间（CI）8.6-13.0），而化疗组为5.6个月（95% CI 5.0-7.0）[风险比0.57（99% CI 0.44-0.73）；P < 0.0001]。

Median OS was 23.7 months (95% CI 19.8-25.6) and 18.7 months (95% CI 16.0-21.8) with Dato-DXd and chemotherapy, respectively [hazard ratio0.79 (95.01% CI 0.64-0.98); P = 0.029].

Dato-DXd和化疗的中位总生存期分别为23.7个月（95%置信区间19.8-25.6）和18.7个月（95%置信区间16.0-21.8）[风险比0.79（95.01%置信区间0.64-0.98）；P = 0.029]。

Treatment-related adverse events (TRAEs) of grade ≥3 were reported in 105 (33%) and 89 (29%) patients who received Dato-DXd and chemotherapy, respectively, and TRAEs led to treatment discontinuation in 14 (4%) and 23 (7%) patients.

分别有105名（33%）和89名（29%）接受Dato-DXd和化疗的患者报告了3级或更高级别的治疗相关不良事件（TRAEs），并且这些不良事件导致14名（4%）和23名（7%）患者停止治疗。

There were no treatment-related deaths in either arm.

在任一组中均未出现与治疗相关的死亡事件。

Conclusions

Dato-DXd demonstrated significantly improved PFS and OS versus chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option.

Dato-DXd 在之前未接受治疗、局部复发无法手术或转移性三阴性乳腺癌患者中，与化疗相比，显著改善了无进展生存期（PFS）和总生存期（OS），这些患者无法接受免疫治疗。

Safety was consistent with the known profile for Dato-DXd.

安全性与Dato-DXd已知的特性一致。