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William J. Gradishar, MD, FACP, FASCO


ESMO 2023: DESTINY-Breast04 Survival Update on T-DXd in HER2-Low Breast Cancer

By: Julia Fiederlein Cipriano, MS
Posted: Tuesday, October 24, 2023

The antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (T-DXd) appeared to confer improved efficacy outcomes and a “generally manageable” safety profile versus standard-of-care monotherapy in patients with HER2-low unresectable and/or metastatic breast cancer, regardless of hormone receptor status, according to Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. These updated 32-month follow-up data from the phase III DESTINY-Breast04 trial, which were presented during the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract 376O), support previous findings.

Patients were randomly assigned in a 2:1 ratio to receive T-DXd (n = 373; hormone receptor–positive: n = 331) or physician’s choice of standard-of-care monotherapy (n = 184; hormone receptor–positive: n = 163). The median durations of survival were longer with T-DXd versus standard-of-care monotherapy in both the full analysis set (progression-free: 8.8 vs. 4.2 months; overall: 22.9 vs. 16.8 months) and the hormone receptor–positive subgroup (progression-free: 9.6 vs. 4.2 months; overall: 23.9 vs. 17.6 months).

The 24-month overall survival rates with T-DXd and standard-of-care monotherapy were 47.3% and 32.0% in the full analysis set and 49.0% and 35.1% in the hormone receptor–positive subgroup, respectively. At 36 months, T-DXd continued to demonstrate higher rates in both groups (full analysis set: 26.2% vs. 16.3%; hormone receptor–positive: 26.5% vs. 16.9%).

Treatment-emergent adverse events of grade 3 or higher were observed in 54.4% of patients treated with T-DXd and in 67.4% of those who underwent standard-of-care monotherapy. The most frequently reported treatment-emergent adverse events were gastrointestinal or hematologic. The exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were 1.2% and 2.6% with T-DXd and standard-of-care monotherapy, respectively. No new adjudicated drug-related interstitial lung disease or pneumonitis events were documented with longer follow-up.

Disclosure: For full disclosures of the study authors, visit

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