DESTINY-Breast09 — Trastuzumab Deruxtecan With or Without Pertuzumab vs Taxane, Trastuzumab, and Pertuzumab in First-Line HER2-Positive Metastatic Breast Cancer

Phase 3 · 2025 · Breast Cancer

Design

Randomized 1:1:1 to trastuzumab deruxtecan plus pertuzumab, trastuzumab deruxtecan plus placebo, or taxane + trastuzumab + pertuzumab (THP) in the first-line setting.

Population

HER2-positive advanced or metastatic breast cancer with no previous chemotherapy or HER2-directed therapy for metastatic disease.

Primary Endpoint

progression-free survival (PFS) by blinded independent central review

Key Result

Median PFS 40.7 mo with T-DXd + pertuzumab vs 26.9 mo with THP (HR 0.56); confirmed response 85.1% vs 78.6%.

Guideline Impact

First-line HER2-positive metastatic breast cancer