TALENT Trial: Neoadjuvant T-DXd for HER2-Low, HR-Positive Breast Cancer

By: Hope Craig, MSPH
Posted: Tuesday, February 7, 2023

In the TALENT study, a team of American researchers reported the first trial to evaluate the safety and activity of neoadjuvant fam-trastuzumab deruxtecan-nxki (T-DXd) alone or in combination with endocrine therapy in patients with HER2-low, hormone receptor (HR)-positive breast cancer. The results were reported by Aditya Bardia, MD, MPH, of the Massachusetts General Hospital Cancer Center, Boston, and colleagues at the 2022 San Antonio Breast Cancer Symposium (Abstract GS2-03).

“T-DXd [with and without] endocrine therapy demonstrates promising clinical activity for [patients] with [hormone receptor–positive breast cancer],” the authors commented.

The study enrolled 58 patients with previously untreated, operable, invasive, early-stage, nonrecurrent, hormone receptor–positive, HER2-low breast cancer tumors > 2 cm between September 2020 to October 2022. In stage I of the trial, patients were randomly assigned on a 1:1 basis to receive T-DXd alone in arm A or in combination with anastrozole in arm B. In February 2022, the number of treatment cycles increased from six to eight cycles for newly enrolled patients or those who had not yet had surgery. Patients in arm B also received a gonadotropin-releasing hormone agonist.

As of early October 2022, 33 patients have completed the study treatment and had surgery, including 17 patients in arm A and 16 patients in arm B. A total of 13 patients are on treatment and 7 are awaiting surgery. A total of 27 patients completed six treatment cycles, and 13 patients completed eight cycles. Five patients left the study before completing therapy. Most patients (n = 46) had baseline HER2 expression of 1+.

In arm A, one patient had a pathologic complete response after eight cycles. The overall response rate in arm A was 75% compared with 63.2% in arm B. The most common grade ≥ 3 adverse effects related to treatment were hypokalemia, diarrhea, neutropenia, fatigue, headache, vomiting, dehydration, and nausea.

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

2022 San Antonio Breast Cancer Symposium