为研究针对人表皮生长因子受体2（HER2）的抗体药物联合物Trastuzumab Deruxtecan在表达HER2的子宫癌肉瘤（UCS）患者中的疗效和安全性，该联合物结合了拓扑异构酶1抑制剂负载。纳入以前接受化疗治疗的HER2免疫组织化学评分≥1+的复发性UCS患者。将患者分为HER2高（免疫组织化学评分≥2+；n = 22）或低（免疫组织化学评分为1+；n = 10）组进行初步和探索性分析。 Trastuzumab deruxtecan以6.4或5.4毫克/千克的剂量每3周静脉注射，直至不能接受的毒性或疾病进展，其剂量修改基于乳腺癌的更新建议的II期剂量为5.4毫克/千克。主要终点是HER2高组的中央审查的客观缓解率。次要终点包括研究人员评估HER2高组的总体缓解率（ORR），HER2低组的ORR，无进展生存期（PFS），总生存期（OS）以及安全性。 HER2高和HER2低组的ORR中央审查分别为54.5%（95% CI，32.2至75.6）和70.0%（95% CI，34.8至93.3），而研究人员评估的分别为68.2%和60.0%。 HER2高和HER2低组的中位PFS和OS分别为6.2和13.3个月和6.7个月和未达到。 20名患者（61%）出现≥3级不良事件。 8名（24％）和1名（3％）患者出现1-2级和3级肺炎/间质性肺疾病。无论HER2状态如何，Trastuzumab Deruxtecan在UCS患者中都具有疗效。安全性的剖面与先前报告的剖面基本一致。通过适当的监测和治疗可以管理毒副作用。

To investigate the efficacy and safety of trastuzumab deruxtecan, an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) with a topoisomerase I inhibitor payload, in patients with uterine carcinosarcoma (UCS) expressing HER2.Patients with recurrent UCS with HER2 immunohistochemistry scores ≥1+ previously treated with chemotherapy were included. Patients were assigned to the HER2-high (immunohistochemistry score ≥2+; n = 22) or low (immunohistochemistry score of 1+; n = 10) groups for primary and exploratory analyses, respectively. Trastuzumab deruxtecan 6.4 or 5.4 mg/kg was administered intravenously once every 3 weeks until unacceptable toxicity or disease progression. Dose modification was based on the updated recommended phase II dose for breast cancer to be 5.4 mg/kg. The primary end point was the objective response rate by central review in the HER2-high group. Secondary end points included the overall response rate (ORR) in the HER2-high group by investigator assessment, ORR in the HER2-low group, progression-free survival (PFS), overall survival (OS), and safety.The ORR by central review in the HER2-high and HER2-low groups were 54.5% (95% CI, 32.2 to 75.6) and 70.0% (95% CI, 34.8 to 93.3) and those by investigator assessments were 68.2% and 60.0%, respectively. The median PFS and OS in the HER2-high and HER2-low groups were 6.2 and 13.3 months and 6.7 months and not reached, respectively. Grade ≥ 3 adverse events occurred in 20 patients (61%). Grades 1-2 and 3 pneumonitis/interstitial lung disease occurred in eight (24%) and one (3%) patient, respectively.Trastuzumab deruxtecan has efficacy in patients with UCS, regardless of HER2 status. The safety profile was generally consistent with that previously reported. Toxicities were manageable with appropriate monitoring and treatment.