PO.RSP01.01 · 监管科学与政策
trastuzumab deruxtecan 治疗 HER2 表达的卵巢癌和子宫内膜癌的真实世界临床结局
Real world clinical outcomes with trastuzumab deruxtecan in HER2 expressing ovarian and endometrial cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：trastuzumab deruxtecan（T-DXd）是一种 HER2 靶向抗体-药物偶联物，基于 DESTINY-PanTumor02 研究，已获 FDA 批准用于治疗 HER2 表达（IHC 2+/3+）的复发性子宫内膜癌（EC）和卵巢癌（OC）。真实世界证据仍然有限。
方法：我们对 2022 年 9 月至 2025 年 11 月间在单一学术医疗中心接受 T-DXd 治疗的所有复发性或转移性 OC 或 EC 患者进行了回顾性研究。主要终点为真实世界客观缓解率（ORR）、疾病控制率（DCR；依据影像学报告）和中位治疗时间（mTOT）。次要终点为中位无进展生存期（mPFS）和总生存期（mOS），采用 Kaplan-Meier 法估计。
结果：33 例患者接受了 T-DXd 治疗（17 例 OC，16 例 EC，表 1）。ORR 和 DCR 分别为 42.4%（14/33）和 66%（22/33），包括 4 例完全缓解和 6 例部分缓解。mTOT 为 5.5 个月（IQR 1.4—7.6）。按 HER2 IHC 评分的 ORR，3+ 为 83%，2+ 为 42%，1+ 为 0%。IHC 1+ 患者的 DCR 为 100%，mTOT 为 7.3 个月（IQR 2.8—18.6）。既往接受 ≤2 线治疗的患者（n=13）ORR 为 69%，而既往接受拓扑异构酶-1 抑制剂（拓扑替康）暴露的患者（n=3）或 BRCA 突变肿瘤患者（n=4）ORR 为 0%。既往接受 mirvetuximab 治疗的患者（n=7）ORR 为 14%，DCR 为 71%。按肿瘤类型：OC 的 ORR 为 47%，EC 为 38%；OC 的 DCR 为 76%，EC 为 56%；OC 的 mTOT 为 5.5 个月（2.5—9.0），EC 为 4.7 个月（0.8—6.9）。OC 的 mPFS 为 6.2 个月（95% CI 2.3—15.8），EC 为 6.0 个月（1.4—7.6）。自 T-DXd 起始计算的 mOS，OC 为 17.3 个月（11.4—27.6），EC 为 10.4 个月（6.3—NR）。
结论：在这一真实世界队列中，T-DXd 显示出与 DESTINY-PanTumor02 一致的良好结局。在 IHC 3+ 肿瘤和更早线使用中观察到较高的缓解率，而在既往拓扑异构酶-1 抑制剂暴露或 BRCA 突变病例中未见缓解。尚需进一步研究以验证缓解预测因素并优化治疗序贯。
基线特征 *HER2 扩增经 FISH 或二代测序检测。**3 例胚系，1 例体细胞。卵巢癌 N=17 子宫内膜癌 N=16 诊断时年龄，均值（标准差）60.8（7.6） 66.9（6.1） 组织学，n（%） 浆液性 13（76%） 8（50%） 透明细胞 2（12%） 1（6%） 癌肉瘤 0 3（18%） 子宫内膜样 1（6%） 4（25%） 其他 1（6%） 0 T-DXd 前的治疗线数，中位数（四分位距/IQR）4（2.5—6.5） 2（2—3） 总治疗线数，中位数（IQR）5（4—9.5） 4（3—4.8） HER2 表达 1+ 4（23%） 1（6%） 2+ 9（53%） 12（75%） 3+ 3（18%） 3（18%） 扩增* 7（41%） 6（37%） BRCA 突变** 2（12%） 2（12%） 同源重组缺陷（HRD）+ 5（29%） 2（12%） 既往拓扑异构酶-1 抑制剂 3（17%） 0 既往聚（ADP-核糖）聚合酶抑制剂（PARP）7（41%） 1（6%） 既往 ADC 7（41%） 2（12%） 子宫内膜亚组 错配修复缺陷（dMMR）- 1（6%） 无特异性分子谱（NSMP）- 1（6%） TP53 突变 - 14（88%） POLE 突变 - 0
查看英文原文 English abstract
Background : Trastuzumab deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate, is an FDA-approved treatment option for HER2-expressing (IHC 2+/3+) recurrent endometrial (EC) and ovarian cancers (OC) based on DESTINY-PanTumor02. Real-world evidence remains limited.
Methods: We conducted a retrospective study of all patients with recurrent or metastatic OC or EC who received T-DXd between September 2022 and November 2025 at a single academic medical center. Primary endpoints were real-world objective response rate (ORR), disease control rate (DCR; by radiology reports) and median time on treatment (mTOT). Secondary endpoints were median progression-free survival (mPFS), and overall survival (mOS), estimated by Kaplan-Meier.
Results : Thirty-three patients received T-DXd (17 OC, 16 EC, Table 1). The ORR and DCR were 42.4% (14/33) and 66% (22/33), including 4 complete responses and 6 partial responses. The mTOT was 5.5 months (mos) (IQR 1.4-7.6). ORR by HER2 IHC score was 83% for 3+, 42% for 2+, and 0% for 1+. Patients with IHC 1+ had a DCR of 100% and mTOT of 7.3 mos (IQR 2.8-18.6). ORR was 69% in patients with ≤2 prior lines (n=13) and 0% among those with prior topoisomerase-1 inhibitor (topotecan) exposure (n=3) or in BRCA-mutated tumors (n=4). Patients with prior mirvetuximab (n=7) had an ORR of 14% and DCR of 71%.By tumor type: ORR was 47% in OC and 38% in EC; DCR was 76% in OC and 56% in EC; mTOT was 5.5 mos (2.5-9.0) in OC and 4.7 mos (0.8-6.9) in EC. The mPFS was 6.2 mos (95% CI 2.3-15.8) for OC and 6.0 mos (1.4-7.6) for EC. mOS from T-DXd start was 17.3 mos (11.4-27.6) for OC and 10.4 mos (6.3-NR) for EC.
Conclusion : In this real-world cohort, T-DXd demonstrated promising outcomes consistent with DESTINY-PanTumor02. High response rates were observed in IHC 3+ tumors and earlier-line use, while no responses were seen with prior topoisomerase-1 inhibitor exposure or in BRCA-mutated cases. Further studies are needed to validate predictors of response and optimize treatment sequencing.
Baseline Characteristics *HER2 amp by FISH or next generation sequencing. **3 germline, 1 somatic. Ovarian cancer N = 17 Endometrial cancer N = 16 Age at diagnosis, mean (std dev) 60.8 (7.6) 66.9 (6.1) Histology, n (%) Serous 13 (76%) 8 (50%) Clear cell 2 (12%) 1 (6%) Carcinosarcoma 0 3 (18%) Endometrioid 1 (6%) 4 (25%) Other 1 (6%) 0 Lines of treatment prior to T-DXd, median (interquartile range/IQR) 4 (2.5-6.5) 2 (2-3) Total lines of treatment, median (IQR) 5 (4-9.5) 4 (3-4.8) HER2 expression 1+ 4 (23%) 1 (6%) 2+ 9 (53%) 12 (75%) 3+ 3 (18%) 3 (18%) Amplification* 7 (41%) 6 (37%) BRCA-mutated** 2 (12%) 2 (12%) Homologous recombination deficient (HRD)+ 5 (29%) 2 (12%) Prior topoisomerase-1 inhibitor 3 (17%) 0 Prior poly(ADP-ribose) polymerase inhibitor (PARP) 7 (41%) 1 (6%) Prior ADC 7 (41%) 2 (12%) Endometrial subgroup Deficient mismatch repair (dMMR) - 1 (6%) No specific molecular profile (NSMP) - 1 (6%) TP53-mutated - 14 (88%) POLE-mutated - 0
利益披露 Disclosure
O. Alomaja, None..
J. F. Silverstein, None..
M. Hajiabbasi, None..
E. Shachar, None..
S. Thaker, None..
B. Karlan, None.
A. Bardia,
AstraZeneca Other, Consultant/advisory relationship.
Daiichi Sankyo Other, Consultant/advisory relationship.
Eli Lilly Other, Consultant/advisory relationship.
Foundation Medicine Other, Consultant/advisory relationship.
Genentech Other, Consultant/advisory relationship.
Gilead sciences Other, Consultant/advisory relationship.
Menarini Other, Consultant/advisory relationship.
Merck Other, Consultant/advisory relationship.
Novartis Other, Consultant/advisory relationship.
Pfizer Other, Consultant/advisory relationship.
Sanofi Other, Consultant/advisory relationship.
G. E. Konecny,
AbbVie Other, Speaker bureau.
AstraZeneca Other, Speaker bureau.
Eli Lilly Other, Research support.
Merck Other, Research support.