Evolving First-Line Treatment Strategies in HER2+ Metastatic Breast Cancer

Current First-Line Treatment Standards

The current standard of care for HER2-positive metastatic breast cancer centers on the CLEOPATRA regimen, which combines docetaxel, trastuzumab, and pertuzumab (THP). This phase 3 trial demonstrated superior progression-free survival of 18.7 months versus 12.4 months compared to the doublet therapy, along with overall survival benefits. The treatment approach typically involves 6 to 8 cycles of induction therapy followed by maintenance with dual antibody therapy.

Treatment modifications are commonly made based on patient characteristics and recent therapy exposure. Patients who progress within 6 months of neoadjuvant or adjuvant therapy are often treated as second-line candidates with alternative strategies like trastuzumab deruxtecan (T-DXd). The addition of endocrine therapy during maintenance, while not part of the original CLEOPATRA protocol, has become standard practice for hormone receptor-positive patients.

Clinical decision-making involves careful consideration of patient factors, with some oncologists extending chemotherapy duration in hormone receptor–negative patients due to the inability to add endocrine therapy for maintenance. The goal is achieving best response through imaging assessment, typically defined as reaching stable disease after initial response, before transitioning to maintenance therapy.