SABCS 2024: HER3-DXd Under Study in HR-Positive, HER2-Negative Early Breast Cancer

By: Vanessa A. Carter, BS
Posted: Wednesday, December 11, 2024

According to Mafalda Oliveira, MD, PhD, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, and colleagues, further strategies to improve outcomes among patients with high-risk hormone receptor (HR)-positive, HER2-negative early breast cancer are needed because of the risk of recurrence with both chemotherapy and endocrine therapy. These researchers investigated HER3-DXd—a potential first-in-class, HER3-directed antibody-drug conjugate—in this patient population and presented their results during the 2024 San Antonio Breast Cancer Symposium (SABCS; Abstract LB1-06).

“Treatment with HER3-DXd, with or without letrozole, resulted in similar pathologic complete response rates to chemotherapy while exhibiting a lower incidence of grade 3 or higher treatment-emergent adverse events,” concluded the investigators. “The ongoing translational analysis will provide further insights into the activity of HER3-DXd in early breast cancer and clarify its potential role as a treatment strategy for high-risk HR-positive, HER2-negative breast cancer.”

This parallel, randomized, open-label study enrolled 122 patients with HR-positive, HER2-negative, inoperable, high-risk early breast cancer. Participants were randomly assigned on a 2:2:1 basis to receive HER3-DXd alone (arm A; n = 50), HER3-DXd plus letrozole (arm B; n = 48), or endocrine therapy plus adjuvant chemotherapy followed by cyclophosphamide and doxorubicin with subsequent paclitaxel (arm C; n = 24).

The residual response rate was higher in arm C (30.4%) than in arm A (18.4%) and arm B (12.5%). In comparison, the objective response rate was lowest in arm C, although not significantly so, according to the investigators.

Among patients in arms A and B, the most common treatment-emergent adverse events were alopecia (52% and 68.8%), diarrhea (42% and 54.2%), and nausea (56% and 72.9%). There was a significant change in the CelTIL (tumor cellularity and infiltrating lymphocytes) score from baseline to cycle two in arms A and B—but not in arm C. Furthermore, this difference seemed to correlate with radiologic response in arms A and B.

Disclosure: For full disclosures of the study authors, visit sabcs.org.

2024 San Antonio Breast Cancer Symposium

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