Nusrat Jahan, MD, is an assistant professor of medicine – hematology & oncology at the O’Neal Comprehensive Cancer Center at The University of Alabama at Birmingham.

Nusrat Jahan, MD, explains the role of T-DXd as the first cytotoxic therapy in patients with HR-positive/HER2-low or -ultralow breast cancer.

Dr Jahan on the Role of T-DXd in HR+/HER2-Low Metastatic Breast Cancer

“[DESTINY-Breast06] is a very important study, and it will change the [breast cancer] practice pattern quite significantly. This study used an antibody-drug conjugate, which is a cytotoxic therapy, but a targeted one…after progression on endocrine therapy.”

Nusrat Jahan, MD, an assistant professor of medicine – hematology & oncology at the O’Neal Comprehensive Cancer Center at The University of Alabama at Birmingham, explained the role of the antibody-drug conjugate (ADC) fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the treatment of patients with hormone receptor–positive, HER2-low or -ultralow metastatic breast cancer.

Findings from the phase 3 DESTINY-Breast06 trial (NCT04494425), which evaluated T-DXd in the respective patient population, has significantly changed the treatment landscape in breast cancer, Jahan began. Data from DESTINY-Breast06 

supported the January 2025 FDA approval of T-DXd

 for the treatment of patients with unresectable or metastatic hormone receptor–positive, HER2-low (immunohistochemistry [IHC] 1+ or 2+/ISH–) or HER2-ultralow (IHC 0 with membrane staining) breast cancer that progressed on 1 or more endocrine therapies in the metastatic setting.

She noted that traditionally, patients have received single-agent chemotherapy after progression on 1 or more lines of endocrine therapy, which was the previous standard of care. Before DESTINY-Breast06, treatments in the second- and third-line settings typically consisted of T-DXd or sacituzumab govitecan-hziy (Trodelvy), Jahan added.

DESTINY-Breast06 compared T-DXd with single-agent chemotherapy and demonstrated significantly improved progression-free survival (PFS) with the ADC; however, overall survival data remained immature, Jahan emphasized. Specifically, patients with HER2-low disease demonstrated a median PFS of 13.2 months (95% CI, 11.4-15.2) vs 8.1 months (95% CI, 7.0-9.0) in the T-DXd and chemotherapy arms, respectively (HR, 0.62; 95% CI, 0.52-0.75; 

 < .001). Jahan concluded that patients in all subgroups on the study experienced improved PFS after receiving T-DXd, which included those with primary or secondary endocrine resistance, small or large burden of disease, previous exposure to CDK4/6 inhibitors, and age.

Nusrat Jahan, MD

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Dr Jahan on the Role of T-DXd in HR+/HER2-Low Metastatic Breast Cancer