The combination of trastuzumab deruxtecan (Enhertu) with pertuzumab (Perjeta) as a first-line treatment for HER2-positive advanced metastatic breast cancer has been shown to reduce the risk for disease progression or death by more than the current standard-of-care treatment.
Sara Tolaney, MD, MPH, of the Dana-Farber Cancer Institute in Boston, presented this finding and other interim results of the phase 3 DESTINY-Breast09 study, at the American Society of Clinical Oncology (ASCO) 2025 annual meeting in Chicago.
“Trastuzumab deruxtecan, or T-DXd, in combination with pertuzumab demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, with a 44% reduction in the risk of disease progression or death when compared to a taxane, trastuzumab, and pertuzumab (THP),” said Tolaney, during her presentation.
New First-line Standard?
Similar results were observed across all patient subgroups, with no new safety signals, Tolaney said.
“These data suggest that T-DXd and pertuzumab may represent a new first-line standard of care for patients with metastatic HER2-positive breast cancer,” she said.
The study randomized 1157 patients to three treatment groups: T-DXd 5.4 mg/kg every three weeks plus placebo, T-DXd-pertuzumab, or a taxane plus trastuzumab with pertuzumab (THP). The interim study readout includes only data from the T-DXd-pertuzumab and the taxane plus trastuzumab with pertuzumab groups.
Pertuzumab + T-Dxd or Standard of Care?
Median progression-free survival (PFS) was 40.7 months in the T-DXd-pertuzumab patients and 26.9 months in the taxane plus trastuzumab with pertuzumab patients (P <.00001).
Tolaney explained that the study was designed to have an interim analysis for PFS after approximately 399 events across the three arms with at least 277 events for comparison. At the time of the interim analysis, she said, only the TDX-pertuzumab and THP groups met the criteria for superiority, a P-value <.00043, which was not met for the comparison of T-DXd plus placebo to THP. The T-DXd-placebo arm remains blinded until the final progression-free survival analysis, Tolaney said.
Twenty-one percent of the patients in the T-DXd-pertuzumab arm had discontinued T-DXd due to adverse events, Tolaney said; 9% of patients elected to continue with trastuzumab and pertuzumab after they discontinued T-DXd.
Among hormone receptor-positive patients, 13.5% in the T-DXd-pertuzumab group and 38% in the THP group elected to add endocrine treatment. At the data cutoff, 46% of the T-DXd-pertuzumab patients and 33% of those in the THP group remained on study treatment. Median follow-up duration was 29 months.
The treatment effect o