Site Editor

William J. Gradishar, MD, FACP, FASCO


ASCO 2022: DESTINY-Breast04 Reports Benefit of T-DXd in HER2-Low Metastatic Breast Cancer

By: Julia Fiederlein
Posted: Tuesday, June 7, 2022

The antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (T-DXd) demonstrated a statistically significant and clinically meaningful progression-free and overall survival benefit versus standard-of-care monotherapy in patients with HER2-low metastatic breast cancer, regardless of hormone receptor status, according to Shanu Modi, MD, of the Memorial Sloan Kettering Cancer Center, New York, and colleagues. The primary results of the multicenter phase III DESTINY-Breast04 trial, which were presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract LBA3), also seemed to support a “generally manageable” safety profile for this HER2-directed therapy, already approved in HER2-high metastatic breast cancer.

“By effectively creating a new category of breast cancer, HER2-low, this trial will redefine how we classify breast cancer and will significantly expand the population of patients who can benefit from HER2-targeted therapy,” said Jane Low Meisel, MD, of Emory University School of Medicine, Atlanta, an ASCO expert in breast cancer.

Patients were randomly assigned in a 2:1 ratio to receive T-DXd (n = 373) or standard-of-care monotherapy (n = 184; capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel). The median durations of progression-free and overall survival were longer with T-DXd than with standard-of-care monotherapy in the full analysis set (progression-free: 9.9 vs. 5.1 months (hazard ratio [HR] = 0.50, P < .0001; overall: 23.4 vs. 16.8 months, HR = 0.64, P = .0010), as well as in the hormone receptor–positive (progression-free: 10.1 vs. 5.4 months, HR = 0.51, P < .0001; overall: 23.9 vs. 17.5 months, HR = 0.64, P = .0028) and hormone receptor–negative subgroups (progression-free: 6.6 vs. 2.9 months, HR = 0.45, P = .0135; overall: 16.6 vs. 10.3 months, HR = 0.63, P = .1732).

Treatment-emergent adverse events of grade 3 or higher were reported in 52.6% of patients treated with T-DXd and 67.4% of those who underwent standard-of-care monotherapy. A total of 12.1% and 0.6% of patients treated with T-DXd and standard-of-care monotherapy, respectively, experienced drug-related interstitial lung disease or pneumonitis.

Disclosure: For full disclosures of the study authors, visit

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.