Dr. Iyengar on the Benefit of Trastuzumab Deruxtecan in Metastatic HER2+ Breast Cancer After T-DM1

Neil M. Iyengar, MD, associate attending physician, medical oncologist, Breast Cancer, Exercise Oncology, Memorial Sloan Kettering Cancer Center, discusses the expanding investigation and role of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive and HER2-low metastatic breast cancer.

Findings from the primary analysis of the phase 3 DESTINY-Breast02 trial (NCT03523585) were presented at the 2022 San Antonio Breast Cancer Symposium, where trastuzumab deruxtecan demonstrated a clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) vs physician’s choice of chemotherapy in patients with HER2-positive metastatic breast cancer who received prior treatment with ado-trastuzumab emtansine (T-DM1; Kadcyla).

Patients treated with trastuzumab deruxtecan experienced a median PFS of 17.8 months (95% CI, 14.3-20.8) per blinded independent central review (BICR) assessment, compared with 6.9 months (95% CI, 5.5-8.4) for physician’s choice of chemotherapy (HR, 0.3589; 95% CI, 0.2840-0.4535; P < .0000001). Additionally, those in the experimental arm achieved a median OS of 39.2 months, compared with 25.6 months for those in the chemotherapy arm (HR, 0.6575; 95% CI, 0.5023-0.8605; P = .0021).

Furthermore, trastuzumab deruxtecan was evaluated vs physician’s choice of chemotherapy in patients with HER2-low metastatic breast cancer during the phase 3 DESTINY-Breast04 trial (NCT03734029). Data presented at the 2022 ASCO Annual Meeting also demonstrated a significant improvement in PFS and OS associated with use of trastuzumab deruxtecan in patients with HER2-low, hormone receptor–positive metastatic breast cancer. Those patients treated with the antibody-drug conjugate experienced a median PFS 10.1 months, compared with 5.4 months for chemotherapy. The median OS for the trastuzumab deruxtecan and chemotherapy arms was 23.9 months and 17.5 months, respectively.

In August 2022, data from DESTINY-Breast04 led to the FDA approval of trastuzumab deruxtecan for the treatment of patients with unresectable or metastatic HER2-low breast cancer. In patients who would have previously been considered HER2-negative, these data demonstrated the benefits of trastuzumab deruxtecan in patients with low levels of HER2 expression, Iyengar explains. This agent represents another option for patients with HER2-low metastatic breast cancer who have been treated with endocrine therapies and 1 to 2 lines of chemotherapy, Iyengar concludes.