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William J. Gradishar, MD, FACP, FASCO


ASCO 2023: Age-Specific Update From DESTINY Trials of T-DXd in Metastatic Breast Cancer

By: Joshua D. Madera, MD
Posted: Friday, June 30, 2023

Efforts to determine the efficacy of treatment with the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (T-DXd) in patients older than age 65 with HER2-positive unresectable or metastatic breast cancer have revealed a favorable benefit-risk profile, according to the age-specific pooled analysis of the DESTINY-Breast01, -02, and -03 studies presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 1006). However, the risk of treatment-related toxicity is slightly increased with this agent in these older individuals, explained Ian E. Krop, MD, PhD, of Yale Cancer Center, New Haven, and colleagues.

A total of 178 patients older than age 65 with HER2-positive unresectable or metastatic breast cancer were recruited from the DESTINY-Breast01 (n = 44), DESTINY-Breast02 (n = 85), and DESTINY-Breast03 (n = 49) studies and compared with patients younger than age 65. Patients from the DESTINY-Breast01 study received previous treatment with ado-trastuzumab emtansine (T-DM1) and had evidence of disease progression. Patients from the DESTINY-Breast02 study were either previously treated with T-DXd or a chemotherapy regimen of their physician’s choice. Patients from the DESTINY-Breast03 trial had received previous combination treatment with trastuzumab and a taxane.

Analysis of the DESTINY-Breast01 data revealed an increased median overall survival in patients older than age 65 (30.9 months) compared with that of those younger than age 65 (28.1 months). A similar trend was observed for this patient population’s progression-free survival (19.4 months vs. 18.1 months, respectively). However, data from the DESTINY-Breast02 and -03 cohorts revealed a decreased median progression-free survival in patients older than age 65 (16.8 months vs. 17.9 months, and 25.1 months vs. 30.4 months, respectively). Furthermore, grade 3 or higher treatment-related adverse events were reported by 65.5% of patients older than age 65 and 53.6% of those younger than age 65.

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