Dr Wagar on the Use of T-DXd in Patients With HER2+ Endometrial Cancer

“I would [advise colleagues] to always think about requesting HER2 testing from the get-go for patients with endometrial cancer. If you’re concerned [that a patient might] have an aggressive phenotype and worried about their response to systemic therapy, having that information ahead of time [could allow you to quickly] switch [therapies based on a patient’s treatment] trajectory.”

Matthew Wagar, MD, a gynecologic oncology fellow in the Department of Obstetrics and Gynecology at the University of Wisconsin School of Medicine and Public Health, discussed the current role of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for patients with HER2-positive endometrial cancer.

Wagar began by stating that the antibody–drug conjugate (ADC) T-DXd, has demonstrated efficacy and received FDA approval for use in the treatment of patients with HER2-positive, pretreated advanced endometrial cancer based on data from the pivotal phase 2 DESTINY-PanTumor02 basket trial (NCT04482309). Notably, in April 2024, the FDA granted accelerated approval to T-DXd for the treatment of patients with unresectable or metastatic HER2-positive solid tumors who have received prior therapy and have no satisfactory treatment alternatives. The pronounced clinical activity observed with this ADC in the endometrial cancer cohort has led to increased interest in its use for this population, although T-DXd also has indications in ovarian and cervical cancers, Wagar added.

Wagar recommended that colleagues perform HER2 testing early in the diagnostic workup for patients with endometrial cancer, particularly in cases with aggressive features. Doing so could facilitate more timely identification of patients who may benefit from HER2-targeted therapy.

Importantly, the DESTINY-PanTumor02 trial defined HER2 positivity using gastric cancer criteria, which differ from those used in uterine cancer, Wagar noted. As such, consistent and effective coordination with pathology teams is essential for ensuring accurate assessment of HER2 status and to avoid missing patients who might be eligible for ADC-based treatment, he concluded.