Dr. Abdou on the Significance of the DESTINY-Breast03 Trial in HER2-Positive Breast Cancer

Yara Abdou, MD, assistant professor, Division of Oncology, Lineberger Comprehensive Cancer Center, UNC Health, UNC School of Medicine, discusses the significance of the phase 3 DESTINY-Breast03 trial (NCT03529110) in HER2-positive breast cancer.

Data from DESTINY-Breast03 demonstrated fam-trastuzumab deruxtecan-nxki (Enhertu) elicited statistically significant and clinically meaningful improvements in progression-free survival (PFS) vs ado-trastuzumab emtansine (Kadcyla; T-DM1), Abdou says. Moreover, all subgroups received a significant benefit in PFS, including visceral disease, hormone receptor status, prior pertuzumab (Perjeta) use, and brain metastases, Abdou explains.

Although the data are not yet statistically significant, trastuzumab deruxtecan also produced an encouraging overall survival benefit, Abdou adds. These results support trastuzumab deruxtecan becoming the standard of care in the second-line setting for metastatic, HER2+ breast cancer, Abdou explains.

The trial generated reassuring safety data, and most of the interstitial lung disease events were grade 1 or 2, with only 2 grade 3 cases, and no grade 4 or 5 incidents, Abdou continues.

Trastuzumab deruxtecan led to a lower rate of intracranial progressive disease, compared with T-DM1, Abdou adds. Larger studies are still needed to examine the activity of trastuzumab deruxtecan in untreated and actively progressing brain metastases, Abdou says. Current evidence remains for tucatinib (Tukysa) combination as the standard-of-care option for patients with brain metastases, Abdou concludes.