Real-World Outcomes of Trastuzumab Deruxtecan (T-DXd) in Patients with Advanced Gynecologic Malignancies
ESMO 2026
J. Silverstein, S. Cullina, N. Baclig, U. Jariwala, F. Battaglin, S. Fragkogianni, K. Viets Layng, J. Mercer, D. Chetram, M. Velez, A. Drakaki, A. Wahner Hendrickson, A. Bardia, G. Konecny
Background
T-DXd, a HER-2 targeted antibody drug conjugate, received tumor agnostic approval for HER2-expressing (IHC 3+) tumors based on the results from the DESTINY-PanTumor02 trial. Despite rapid clinical adoption in gynecologic cancers, real world data remains limited. We sought to assess the real-world outcomes of T-DXd in patients with gynecologic cancers.
Methods
We used the Tempus Lens platform to query de-identified patient records in the multimodal database to identify patients (pts) who received T-DXd and had clinical sequencing using Tempus xT (DNA) and/or xR (RNA) assays. Risk set–adjusted (RSA) Kaplan–Meier methods were used to evaluate real-world progression-free survival (rwPFS), defined as the time from T-DXd initiation to disease progression, death from any cause or last known follow up. rwPFS was stratified by HER2 IHC. Hazard ratios (HR) were estimated using Cox proportional hazard models and compared using the log-rank test.
Results
We identified 81 pts with gynecologic malignancies treated with T-DXd from July 2020 to February 2026 with a median follow-up time of 19.9 months (mos). Baseline characteristics are summarized in Table 1. The median rwPFS was 7.1 mos (95% CI: 4.8-11.6). By tumor type, median rwPFS was 6.5 mos (95% CI: 4.2- 14.0) in ovarian and 8.6 mos (95% CI: 4.8 - 16.2) in endometrial cancer. A trend toward longer rwPFS was observed with increasing HER2 protein expression (N = 36), with median rwPFS of 13.9 mos (95% CI: 6.8-NA) in HER2 IHC 3+ tumors and 7.4 mos (95% CI: 4.2-16.2) in HER2 IHC 2+ tumors (p=0.09). In a multivariable Cox model including age, line of therapy, prior PARP inhibitor use, TP53 mutation status, and HER2 IHC status (2+ vs 3+), only HER2 IHC 2+ (vs 3+) was associated with worse outcomes (HR 3.54, 95% CI 1.00–12.5; p=0.050).
Table 1. Baseline Characteristics
| Characteristic | Patients with Gynecologic Cancers (N=81) |
|---|---|
| Median age at T-DXd initiation (IQR) | 65 (61, 72) |
| Cancer type: Ovarian/fallopian/primary peritoneal, n (%) | 32 (39.5%) |
| Cancer type: Endometrial/uterine, n (%) | 43 (53.0%) |
| Cancer type: Cervix/vulva, n (%) | 6 (7.4%) |
| HER2 IHC: 0, n (%) | 1 (2.5%) |
| HER2 IHC: 1+, n (%) | 3 (7.5%) |
| HER2 IHC: 2+, n (%) | 23 (58%) |
| HER2 IHC: 3+, n (%) | 13 (33%) |
| HER2 IHC: missing, n (%) | 41 (50.6%) |
| T-DXd line of therapy: ≤ 2 lines, n (%) | 35 (43.2%) |
| T-DXd line of therapy: 3 lines or more, n (%) | 39 (48.1%) |
| Prior PARP inhibitor, n (%) | 13 (16%) |
| Prior antibody-drug conjugate, n (%) | 5 (6.2%) |
Conclusions
In this real-world cohort, T-DXd demonstrated encouraging clinical activity, with the longest rwPFS observed in tumors with HER2 IHC 3+ expression, supporting its continued use in pts with gynecologic cancers.
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