T-DXd May be ‘Practice Changing’ in HER2+ Gynecologic Cancers


Trastuzumab deruxtecan appears to elicit ‘impressive’ responses among patients with HER2-positive gynecologic cancers regardless of immunohistochemistry in the phase 2 DESTINY-PanTumor02 trial.

Fam-trastuzumab deruxtecan-nxki (Enhertu) is on the “cusp of changing practice” for gynecologic cancers harboring HER2-positive tumors, according to Ritu Salani, MD.

CancerNetwork® spoke with Salani, the Gynecologic Oncology Fellowship Director at University of California Los Angeles Health and the Gynecologic Oncology editorial board member for the journal ONCOLOGY®, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting about “impressive” findings from the phase 2 DESTINY-PanTumor02 trial (NCT04482309) investigating the activity of trastuzumab deruxtecan across several types of HER2-positive solid tumors including gynecologic malignancies.

The overall response rate among patients with cervical cancer who received the agent (n = 40) was 50.0%, 57.5% for endometrial cancer (n = 40), and 45.0% for ovarian cancer (n = 40). This included complete responses in 5.0%, 17.5%, and 10.0%, as well as partial responses in 45.0%, 40.0%, and 35.0% in each respective arm.


The other thing that's on the horizon is the role of HER2 antibody-drug conjugate, trastuzumab deruxtecan, which has really made an impact in breast cancer. We saw a trial of pan tumor testing, which really focused on gynecologic cancers: cervical cancer, ovarian cancer, and endometrial cancer were studied. They looked at IHC expression, really looking at patients with all-comers, but also highlighting the IHC 3+ and 2+ [patients]. And the response rates—these were mostly heavily pretreated patients—are really very impressive.

[It is a] small study. We need to understand what these patients received previously and how standard these patients were. But in the patients [who are] HER2-positive, whether it was IHC 2 or 3, we saw response rates in these heavily pretreated patients that we've not seen before. This is something that's really exciting. It's definitely on the cusp of changing practice. It's already changed practices in other areas, and it's only a matter of time before it does in gynecologic malignancies. I'm hoping that this [agent] will receive disease site agnostic or biomarker approval as we learn more about it.


Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results. J Clin Oncol. 2023;41(suppl 17):LBA3000.

Recent Videos
Although no responses were observed in 11 patients receiving abemaciclib monotherapy, combination therapies with abemaciclib may offer clinical benefit.
Findings show no difference in overall survival between various treatments for metastatic RCC previously managed with immunotherapy and TKIs.
An epigenomic profiling approach may help pick up the entire tumor burden, thereby assisting with detecting sarcomatoid features in those with RCC.
Investigators are assessing the use of IORT in patients with borderline resectable or unresectable pancreatic cancer as part of the phase 2 PACER trial.
The approval for epcoritamab in patients with R/R follicular lymphoma was supported by encouraging efficacy findings from the phase 1/2 EPCORE NHL-1 trial.
A phase 1/2 trial assessed the use of menin inhibitor DSP-5336 in patients with acute leukemia overexpressing HOXA9 and MEIS1.
A phase 1 trial assessed the use of PSCA-directed CAR T cells in patients with metastatic castration-resistant prostate cancer.
A pooled analysis trial assessed the impact of acalabrutinib in patients with chronic lymphocytic leukemia across treatment lines.
Findings from a phase 1 study may inform future trial designs intended to yield longer responses with PSCA-targeted CAR T cells.
A phase 1 trial assessed the use of PSCA-directed CAR T cells in patients with metastatic castration-resistant prostate cancer.
Related Content