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The EMA has validated a Type II variation application for trastuzumab deruxtecan plus pertuzumab in first-line HER2-positive metastatic breast cancer.
The European Medicines Agency (EMA) has validated the Type II variation marketing authorization application for fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in combination with pertuzumab (Perjeta) for the first-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer, marking the completion of the application and commencement of the scientific review process.1
The application is supported by
“This validation in the European Union [EU] is an important step in moving us closer to offering T-DXd in combination with pertuzumab as a potential new first-line treatment option for patients with HER2-positive metastatic breast cancer,” Ken Takeshita, MD, global head of R&D at Daiichi Sankyo, expressed in a news release.1 “Following the recent approval in the US for this indication, we look forward to working closely with the EMA to bring T-DXd to eligible patients in the EU who may benefit from improved outcomes in a setting where the standard of care has not changed in more than a decade.”
In the multicenter, open-label phase 3 DESTINY-Breast09 trial, adults with pathologically confirmed advanced or metastatic HER2-positive breast cancer were randomly assigned in a 1:1:1 fashion to 1 of 3 treatment arms.2,3 Patients received T-DXd at 5.4 mg/kg every 3 weeks plus placebo (n = 387), T-DXd plus pertuzumab (n = 383), or investigator’s choice of a taxane (paclitaxel or docetaxel) in combination with trastuzumab and pertuzumab (THP; n = 387).
The primary end point was PFS assessed by blinded independent central review. Overall survival (OS) served as a key secondary end point. Additional secondary end points included PFS per investigator assessment, objective response rate, duration of response, and safety/tolerability.
Eligible patients were 18 years or older with no prior chemotherapy or HER2-directed therapy for advanced/metastatic disease; patients could have received up to 1 prior line of endocrine therapy in the metastatic setting. Key inclusion criteria also required adequate organ and bone marrow function and an ECOG performance status of 0 or 1. Random assignment was stratified by de novo vs recurrent disease, hormone receptor status (positive vs negative), and the presence vs absence of detectable PIK3CA mutations.
The safety findings for T-DXd plus pertuzumab in DESTINY-Breast09 were consistent with the established profiles of the individual agents.2 In the T-DXd and THP arms, respectively, the most common any-grade treatment-emergent adverse effects (TEAEs) were nausea (71.1% vs 28.8%), diarrhea (55.9% vs 54.2%), neutropenia (48.8% vs 44.5%), and fatigue (48.3% vs 34.6%). The most frequent grade 3 or higher TEAEs included neutropenia (23.9% vs 33.2%), hypokalemia (10.2% vs 1.6%), and anemia (8.4% vs 3.7%).
