ASCO 2025 – Metastatic Breast Cancer Summary

ASCO 2025 – Metastatic Breast Cancer Summary

HR+/HER2- mBC: Moving Beyond CDK4/6 Inhibitors
-- CAPItello-291: Capivasertib + fulvestrant improved PFS in endocrine-resistant HR+ mBC.
-- CAMBRIA-1: Camizestrant (oral SERD) showed activity in ESR1-mutated patients.
-- innovaTV 301: Tucatinib + trastuzumab demonstrated efficacy in HER2-low/HR+ disease.

HER2+ mBC: Post-T-DXd Sequencing and New Standards
-- DESTINY-Breast09: T-DXd + pertuzumab significantly improved first-line PFS vs standard THP.
-- Median PFS: 40.7 vs 26.9 months (HR = 0.56; P < .00001)
-- 2-year PFS: 70.1% vs 52.1%
-- ORR: 85.1% vs 78.6%; CR rate: 15.1% vs 8.5%
-- ILD/pneumonitis in ~12% (Grade 5 ~0.5%)
-- Suggests T-DXd + P may become new first-line standard in HER2+ mBC.
-- HER2CLIMB-05: Tucatinib + T-DXd vs T-DXd alone – early signals suggest CNS control benefits.

PATINA Trial – HER2+ HR+ Maintenance Strategy
-- Adding palbociclib + endocrine therapy to trastuzumab + pertuzumab maintenance did not improve PFS (HR = 0.93).
-- Calls into question the role of CDK4/6 inhibitors in HER2+ maintenance settings.

TNBC Developments
-- ASCENT-04: Sacituzumab govitecan + checkpoint inhibitor showed promise in PD-L1+ TNBC.
-- ADC-immunotherapy combinations are under investigation to overcome resistance.

Precision Oncology & Biomarkers
-- ctDNA monitoring gaining traction for tracking early resistance and guiding therapy.
-- Key actionable biomarkers include PIK3CA, ESR1, BRCA, and HER2-low/ultralow.
Practice Takeaways:
-- DESTINY-Breast09 may redefine first-line standard of care in HER2+ mBC.
-- PATINA results suggest a more cautious approach to CDK4/6 inhibitors in HER2+ HR+ patients.
-- HER2-low continues to emerge as a treatable subtype with specific ADC strategies.
-- ADCs dominate mTNBC care, with new combo strategies in testing.
-- Molecular profiling and ctDNA monitoring are increasingly essential in managing mBC.