Dr Meric-Bernstam on the Efficacy of T-DXd in HER2-Expressing Solid Tumors

Funda Meric-Bernstam, MD, chair, the Department of Investigational Cancer Therapeutics–the Phase I Program, medical director, the Institute for Personalized Cancer Therapy (IPCT), the Nellie B. Connally Chair in Breast Cancer, the University of Texas MD Anderson Cancer Center, discusses results from the phase 2 DESTINY-PanTumor02 trial (NCT04482309) of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with HER2-expressing solid tumors.

The open-label, multicenter study evaluated the efficacy of T-DXd in patients with advanced HER2-expressing solid tumors who were ineligible for curative therapy following progression on one or more systemic therapies. Tumor types included endometrial cancer, cervical cancer, ovarian cancer, biliary tract cancer, pancreatic cancer, and bladder cancer. A total of 267 patients received T-DXd at a dose level of 5.4 mg/kg every 3 weeks.

In the overall population, T-DXd elicited an overall objective response rate (ORR) of 37.1%, with a median duration of response (DOR) of 11.3 months, Meric-Bernstam reports. The median progression-free survival (PFS) was 6.9 months, and the median overall survival (OS) was 13.4 months. Further efficacy analysis according to immunohistochemistry (IHC) expression level showed that patients with IHC 3+ tumors experienced an ORR of 61.3%, a median duration of response (DOR) of 22.1 months, a median PFS of 11.9 months, and a median OS of 21.1 months, Meric-Bernstam adds. Comparatively, patients with IHC 2+ expression had an ORR of 27.2%, median DOR of 9.8 months, median PFS of 5.4 months, and a median OS of 12.2 months. Notably, clinically meaningful response rates were seen with the agent across all tumor types.

These findings highlight the potential of T-DXd to serve as a tumor-agnostic treatment for HER2-expressing malignancies, and offer a new therapeutic option for patients who have progressed after previous systemic treatments, Meric-Bernstam concludes.