Trastuzumab deruxtecan in hormone receptor-positive, HER2-low/-ultralow metastatic breast cancer (DESTINY-Breast06): outcome analyses by time to progression on prior first-line endocrine therapy with CDK4/6 inhibitor and baseline burden of disease.

We report additional analyses exploring outcomes for patients with characteristics that affect prognosis.

我们报告了额外的分析，探讨了影响预后的患者特征对结果的影响。

patients_and_methods

Patients were randomly assigned 1 : 1 to receive T-DXd (5.4 mg/kg) once every 3 weeks or TPC.

患者被随机1:1分配接受T-DXd (5.4 mg/kg) 每3周一次或TPC。

Subgroups were specified post hoc from the intent-to-treat population (N = 866).

事后从意向治疗人群中指定了亚组(N = 866)。

Outcomes were PFS, objective response rate(ORR), and duration of response (DOR) by blinded independent central review via RECIST 1.1.

结局指标包括无进展生存期（PFS）、客观缓解率（ORR）和缓解持续时间（DOR），这些数据通过 RECIST 1.1 标准由盲法独立中心评审得出。

Time from randomization until second progression or death (PFS2) by investigator and safety were also assessed.

研究者还评估了从随机分组到第二次进展或死亡的时间（PFS2）以及安全性。

Results

Within subgroups, baseline disease characteristics and prior therapies were balanced across treatments.

在各亚组中，基线疾病特征和先前的治疗在不同治疗组之间是均衡的。

Median PFS (95% confidence interval) favored T-DXd versus TPC regardless of time to progression (TTP) on prior first-line endocrine therapy (ET) + cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i): <6 months: 14.0 (11.2-15.9) versus 6.5 (4.2-8.4) months for T-DXd versus TPC; 6-12 months: 13.2 (8.6-16.4) versus 6.9 (4.3-10.4) months; >12 months: 12.9 (9.8-17.1) versus 8.2 (6.9-10.9) months.

中位无进展生存期（95% 置信区间）在先前一线内分泌治疗（ET）+细胞周期依赖性激酶4和6抑制剂（CDK4/6i）的进展时间（TTP）小于6个月、6-12个月和大于12个月的情况下，T-DXd均优于TPC：TTP小于6个月时，T-DXd与TPC的中位无进展生存期分别为14.0个月（95% CI 11.2-15.9）和6.5个月（95% CI 4.2-8.4）；TTP在6-12个月时，分别为13.2个月（95% CI 8.6-16.4）和6.9个月（95% CI 4.3-10.4）；TTP大于12个月时，分别为12.9个月（95% CI 9.8-17.1）和8.2个月（95% CI 6.9-10.9）。

A consistent PFS benefit with T-DXd over TPC was observed for patients with primary or secondary endocrine resistance, and across indicators of high or low disease burden (defined as visceral/non-visceral disease, presence/absence of liver metastases, three or more/less than three disease sites, and >median/≤median baseline tumor size).

对于原发性或继发性内分泌抵抗的患者，以及高疾病负担或低疾病负担（定义为内脏/非内脏疾病、有/无肝转移、三个或更多/少于三个病灶，以及>中位数/≤中位数基线肿瘤大小）的患者，T-DXd与TPC相比，观察到一致的无进展生存（PFS）获益。

In all subgroups, confirmed ORR favored T-DXd (36.7% to 67.7%) versus TPC (16.7% to 37.5%), and median DOR (confirmed response) was longer with T-DXd.

在所有亚组中，确认的客观缓解率（ORR）均倾向于T-DXd（36.7%至67.7%）而非TPC（16.7%至37.5%），且T-DXd的中位持续缓解时间（DOR，确认的反应）更长。

T-DXd also prolonged PFS2 versus TPC across subgroups.

T-DXd 还延长了与 TPC 相比的第二次无进展生存期（PFS2），这一效果在各个亚组中均有所体现。

Safety profiles of T-DXd and TPC in subgroups were consistent with the overall safety population.

T-DXd 和 TPC 在亚组中的安全性特征与整体安全性人群一致。

Conclusions

These data support T-DXd as a broadly efficacious treatment for patients with HR-positive, HER2-low/-ultralow mBC after one or more ETs, regardless of TTP on prior first-line ET + CDK4/6i, endocrine resistance, or disease burden.

这些数据支持T-DXd作为一种广泛有效的治疗方法，适用于接受过一次或多次内分泌治疗（ET）的HR阳性、HER2低/极低转移性乳腺癌（mBC）患者，无论其在先前一线ET+CDK4/6抑制剂治疗中的疾病进展时间（TTP）、内分泌治疗抵抗或疾病负担如何。