DESTINY-Breast09: T-DXd Plus Pertuzumab Leads in HER2+ Breast Cancer
The DESTINY-Breast09 trial showed that first-line fam-trastuzumab deruxtecan plus pertuzumab improved progression-free survival in HER2+ metastatic breast cancer.
3D rendering of breast cancer: © Giovanni Cancemi - stock.adobe.com
Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta) led to a highly statistically significant and clinically meaningful benefit in progression-free survival (PFS) vs taxane, trastuzumab (Herceptin) and pertuzumab (THP) for the treatment of patients with first-line HER2-positive (HER2+) metastatic breast cancer, according to high-level findings from an analysis of the phase 3 DESTINY-Breast09 study (NCT04784715).1
“This is the first trial in more than a decade to demonstrate superior efficacy across a broad HER2-positive metastatic breast cancer patient population compared to the current 1st-line standard of care. This is a significant milestone for patients and sets the foundation for [T-DXd] in combination with pertuzumab as an important treatment option in the first-line HER2-positive setting,” said Susan Galbraith, executive vice president of oncology hematology research and development, AstraZenca, in a press release.
The PFS benefit was observed across all patient subgroups. Data for the secondary end point of overall survival (OS) was not mature at the time of this planned interim analysis; however, an early positive trend has been observed in the T-DXd combination arm.
Data from the analysis will be presented at an upcoming medical meeting. A second arm assessing T-DXd monotherapy vs THP remains blinded and will continue to final PFS analysis.
Regarding safety, the safety profile of the T-DXd/pertuzumab combination was consistent with the known profiles of each therapy alone.
“The results from DESTINY-Breast09 reinforce the importance of effectively targeting HER2 to achieve durable disease control early in the treatment of HER2-positive metastatic breast cancer. Building on the positive results seen with [T-DXd] in the second-line setting, these new findings suggest that starting treatment with [T-DXd] in combination with pertuzumab at the time of metastatic diagnosis delays disease progression, postponing the time until additional treatment may be needed,” said Ken Takeshita, global head of research and development, Daiichi Sankyo, in the press release.
T-DXd is FDA-approved for the second-line treatment of HER2+ breast cancer based on data from the DESTINY-Breast03 study (NCT03529110).
About DESTINY-Breast09
DESTINY-Breast09 is a phase 3 study. Patients were randomized to 1 of 3 treatment arms: T-DXd plus placebo, T-DXd plus pertuzumab, or THP.2
The study’s primary end point is PFS, and secondary end points include OS, objective response rate, duration of response, time to second PFS, and patient-reported treatment tolerability.
A total of 1157 patients were enrolled across 284 global sites. Patients aged 18 and older were required to have HER2+ metastatic breast cancer, an ECOG performance status of 0 or 1, and adequate organ and marrow function.
The study has an estimated primary completion date of July 24, 2025.
