Dr LeVee on T-DXd in HER2+ Breast Cancer With/Without Brain Metastases

“T-DXd [displayed] responses in patients with baseline brain metastases, both in terms of overall PFS and CNS PFS. The ORRs [also] showed encouraging activity.”

Alexis LeVee, MD, chief Hematology & Medical Oncology fellow at City of Hope, discussed findings from the phase 3b/4 DESTINY-Breast12 study (NCT04739761) evaluating fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the treatment of patients with HER2-positive advanced or metastatic breast cancer with or without brain metastases.

DESTINY-Breast12 required that patients had received 2 or less lines of prior therapy in the metastatic setting, LeVee began. Notably, patients could not have received prior tucatinib (Tukysa), as this agent has been shown to have central nervous system (CNS) activity, she added. The primary end point of the study was progression-free survival (PFS). Secondary end points included CNS PFS, overall survival, CNS overall response rate (ORR), and safety and tolerability.

LeVee noted that T-DXd produced encouraging activity in terms of CNS PFS, overall PFS, and ORR. The median PFS in the overall population (n = 263) was 17.3 months (95% CI, 13.7-22.1). The 12-month PFS rates among those with active (n = 106), untreated (n = 39), and previously treated or progressing (n = 67) brain metastases were 59.6% (95% CI, 49.0%-68.7%), 47.0% (95% CI, 29.6%-62.7%), and 66.7% (95% CI, 53.4%-62.7%), respectively.

The 12-months CNS PFS rate in the overall population was 58.9% (95% CI, 51.9%-65.3%). The 12-month CNS PFS rates among patients with stable (n = 157) and active (n = 106) brain metastases were 57.8% (95% CI, 48.2%-66.1%) and 60.1% (95% CI, 49.2%-69.4%), respectively.

These data indicate that T-DXd can be used in patients with baseline brain metastases, LeVee explained. This adds an additional regimen for these patients beyond that used in the phase 2 HER2CLIMB study (NCT02614794), LeVee concluded.