US Food and Drug Administration Approval Summary: Trastuzumab Deruxtecan for the Treatment of Adult Patients With Hormone Receptor-Positive, Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2-Low or Human Epidermal Growth Factor Receptor 2-Ultralow Breast Cancer.

patients_and_methods

Approval was based on DESTINY-Breast06, a randomized, open-label, multicenter trial of 866 patients with HR-positive breast cancer, including 713 patients with HER2-low and 153 with HER2-ultralow tumors.

该批准基于DESTINY-Breast06试验，这是一项随机、开放标签、多中心试验，涉及866名激素受体阳性乳腺癌患者，其中713名患者为HER2低表达，153名为HER2超低表达。

Patients were required to have progressed on previous ET and must not have received chemotherapy in the metastatic setting.

患者必须在之前的内分泌治疗中进展，并且在转移性环境中未接受过化疗。

Random assignment was 1:1 to T-DXd or investigator's choice of chemotherapy (paclitaxel, nab-paclitaxel, or capecitabine).

随机分配按照1:1的比例，接受T-DXd治疗或研究者选择的化疗方案（紫杉醇、白蛋白结合紫杉醇或卡培他滨）。

Previous CDK4/6 inhibitor treatment, previous taxane use in the (neo)adjuvant setting, and HER2 status (IHC2+/ISH- v 1+ v IHC 0 with membrane staining) were stratification factors.

之前的CDK4/6抑制剂治疗、之前的紫杉烷类药物在新辅助或辅助治疗中的使用，以及HER2状态（IHC2+/ISH-与1+，以及IHC 0伴膜染色）是分层因素。

Results

There was a statistically significant improvement in progression-free survival(PFS) by blinded independent central review (BICR) in the HER2-low population of 13.2 months (95% CI, 11.4 to 15.2) in the T-DXd arm and 8.1 months (95% CI, 7.0 to 9.0) in the chemotherapy arm (hazard ratio[HR], 0.62 [95% CI, 0.52 to 0.75], P < .0001).

在HER2低表达人群中，通过盲法独立中心评审（BICR）评估的无进展生存期（PFS）有统计学显著性改善，T-DXd组为13.2个月（95%置信区间，11.4至15.2个月），化疗组为8.1个月（95%置信区间，7.0至9.0个月）（风险比[HR]为0.62 [95%置信区间，0.52至0.75]，P < .0001）。

The trial also met its key secondary end point, PFS by BICR in the overall population, with a HR of 0.64 (95% CI, 0.54 to 0.76, P < .0001).

该试验还达到了其主要次要终点，即通过BICR评估的整体人群的无进展生存期（PFS），其风险比（HR）为0.64（95%置信区间，0.54至0.76，P < .0001）。

Conclusions

T-DXd is a new treatment option for patients with hormone receptor-positive, unresectable or MBC with HER2-low or HER2-ultralow tumors who have experienced progression on ET.

T-DXd为激素受体阳性、不可切除或转移性乳腺癌（MBC）患者提供了一种新的治疗选择，这些患者具有HER2低表达或HER2超低表达肿瘤，并且在内分泌治疗（ET）后疾病进展。

This is the first indication specifying the category of HER2-ultralow expression in breast cancer, and an assay to select patients for this category was approved contemporaneously.

这是首次明确指出乳腺癌中HER2超低表达的类别，并且同时批准了一种用于筛选该类别患者的检测方法。