Based on results from the DESTINY-Breast03 trial, trastuzumab deruxtecan (T-DXd; Enhertu) became the preferred, guideline-supported, second-line therapy for HER2-positive metastatic breast cancer, regardless of hormone receptor (HR) status, replacing trastuzumab emtansine (T-DM1; Kadcyla) as the default standard.
However, findings from DESTINY-Breast09 have led to a shift.
In that trial, first-line T-DXd combined with pertuzumab (Perjeta) significantly improved progression-free survival (PFS) in HER2-positive locally advanced or metastatic breast cancer, regardless of HR status, compared with the standard first-line treatment of trastuzumab (Herceptin) plus pertuzumab and a taxane (THP).
Thus, T-DXd has become a frontline option alongside THP, leading to the question of what comes next.
"There's a lot of movement," Erika Hamilton, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee, told MedPage Today. "I think the biggest question right now is whether everyone is going to receive trastuzumab deruxtecan in combination with pertuzumab up front, or whether some patients are still appropriate for taxane, trastuzumab, and pertuzumab."
