Enhertu (trastuzumab deruxtecan) plus Perjeta (pertuzumab) demonstrated highly clinically meaningful improvement in progression-free survival versus THP as first-line therapy for HER2 positive metastatic breast cancer- Daiichi Sankyo + AstraZeneca

Positive topline results from a planned interim analysis of the DESTINY-Breast09 phase III trial showed Enhertu (trastuzumab deruxtecan) in combination with Perjeta  (pertuzumab) demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to taxane, trastuzumab and pertuzumab (THP) as a first-line treatment for patients with HER2 positive metastatic breast cancer.

DESTINY-Breast09 is a global, multicenter, randomized, open-label, phase III  trial evaluating the efficacy band safety  of Enhertu (5.4 mg/kg) either alone or in combination with Perjeta()pertuzumab) versus standard of care THP (a taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab) as a first-line treatment in patients with HER2 positive metastatic breast cancer (NCT04784715).  Patients were randomized 1:1:1 to receive either  Enhertu  monotherapy with a pertuzumab matching placebo; Enhertu in combination with pertuzumab; or THP. Randomization was stratified by prior treatment (de novo metastatic disease versus progression from early-stage disease), hormone receptor (HR) status and PIK3CA mutation status. The primary endpoint of DESTINY-Breast09 is PFS as assessed by blinded independent central review in both the Enhertu monotherapy and Enhertu combination arms. Secondary endpoints include investigator-assessed PFS, OS, objective response rate, duration of response, pharmacokinetics and safety. DESTINY-Breast09   enrolled 1,157 patients across multiple sites in Africa, Asia, Europe, North America and South America.

The PFS improvement was seen across all pre-specified patient subgroups with Enhertu in combination with pertuzumab. The key secondary endpoint of overall survival (OS) was not mature at the time of this planned interim analysis; however, interim OS data showed an early trend favoring the Enhertu combination compared to THP. The second arm assessing  Enhertu monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis.

The safety profile of Enhertu  in combination with pertuzumab was consistent with the known profiles of each individual therapy. Data from the combination arm of DESTINY-Breast09 will be presented at an upcoming medical meeting and shared with regulatory authorities.

 “The results of DESTINY-Breast09 reinforce the importance of effectively targeting HER2 to achieve durable disease control early in the treatment of HER2 positive metastatic breast cancer,” said Dr. Ken Takeshita,  Global Head, R&D, Daiichi Sankyo. “Building on the positive results seen with ENHERTU in the second-line setting, these new findings suggest that starting treatment with ENHERTU in combination with pertuzumab at the time of metastatic diagnosis delays disease progression, postponing the time until additional treatment may be needed.”

“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 first-line standard of care,” said Dr.  Susan Galbraith,  Executive Vice President, Oncology Hematology R&D, AstraZeneca. “This is a significant milestone for patients and sets the foundation for ENHERTU in combination with pertuzumab as an important treatment option in the first-line HER2 positive setting.”