Abstract 1402: Real world clinical outcomes with trastuzumab deruxtecan in HER2 expressing ovarian and endometrial cancer.

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. Citation Format: Oladunni Alomaja, Jordyn F. Silverstein, Maryam Hajiabbasi, Eliya Shachar, Shivani Thaker, Beth Karlan, Aditya Bardia, Gottfried E. Konecny. Real world clinical outcomes with trastuzumab deruxtecan in HER2 expressing ovarian and endometrial cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1402.