Personalizing First-Line HER2+ mBC Treatment: Balancing Tolerability, Convenience, and Patient Goals in HER2+ mBC

Clinical Decision-Making and Risk Assessment

Clinical integration of new first-line strategies requires careful patient selection based on multiple factors including recent treatment exposure, disease burden, and patient preferences. Patients progressing soon after adjuvant therapy, those with large disease burden, or patients with liver metastases and elevated liver function tests represent ideal candidates for T-DXd therapy due to its high response rates across all treatment lines.

Age, performance status, comorbidities, hormone receptor status, and patient preferences all influence treatment decisions. The emergence of hormone receptor status as a key discriminating factor has become more apparent following PATINA trial results, suggesting different optimal approaches for hormone receptor positive versus negative disease. More frequent imaging requirements (every 6 weeks) and heightened awareness for interstitial lung disease also factor into decision-making.

Specific attention to pulmonary comorbidities becomes crucial given ILD risks, though lung metastases alone don't preclude T-DXd use. High-resolution chest CT imaging and collaboration with pulmonology and radiology colleagues are essential for early interstitial lung disease detection. Patient counseling must address the permanent discontinuation requirement for grade 2 or higher symptomatic pneumonitis, emphasizing the importance of early asymptomatic detection.