FDA approves fam-trastuzumab deruxtecan-nxki with pertuzumab for unresectable or metastatic HER2-positive breast cancer
Regulatory approval: On Dec 15, 2025, the FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu) plus pertuzumab for first-line treatment of adults with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved test. Approval was supported by DESTINY-Breast09, where the combination improved BICR-assessed PFS versus taxane/trastuzumab/pertuzumab (THP). The FDA also approved PATHWAY 4B5 IHC and HER2 Dual ISH companion diagnostics.
FDA approval: fam-trastuzumab deruxtecan-nxki + pertuzumab in 1L HER2-positive metastatic breast cancer
Type: Regulatory approval
Date: 2025-12-15
Agency: FDA
The FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu) in combination with pertuzumab for first-line treatment of adults with unresectable or metastatic HER2-positive breast cancer (IHC 3+ or ISH+) as determined by an FDA-approved test.
The FDA also approved the PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody and HER2 Dual ISH DNA Probe Cocktail as companion diagnostic devices to select eligible patients.
Supporting evidence (DESTINY-Breast09; NCT04784715)
DESTINY-Breast09 was a randomized, three-arm, multicenter, global trial (N=1157) enrolling adults with HER2-positive advanced/metastatic breast cancer without prior chemotherapy or HER2-targeted therapy for advanced/metastatic disease (neoadjuvant/adjuvant HER2 therapy allowed if >6 months before metastatic diagnosis). Patients were randomized to fam-trastuzumab deruxtecan-nxki 5.4 mg/kg + pertuzumab (N=383), THP (taxane + trastuzumab + pertuzumab; N=387), or an investigational therapy (N=387).
Primary endpoint PFS (BICR, RECIST v1.1): median PFS 40.7 months vs 26.9 months (HR 0.56, 95% CI 0.44–0.71; p<0.0001) for fam-trastuzumab deruxtecan-nxki + pertuzumab vs THP. Confirmed ORR was 87% vs 81%.
OS data were not mature at PFS analysis (126 deaths [16%] across both study arms).
Label notes
Prescribing information includes warnings/precautions for neutropenia and left ventricular dysfunction. Recommended dosing: Cycle 1 Day 1 fam-trastuzumab deruxtecan-nxki 5.4 mg/kg then pertuzumab 840 mg; subsequent cycles pertuzumab 420 mg, every 3 weeks.
The review used Project Orbis and RTOR, and received priority review and breakthrough designation.