Choosing Upfront Therapy Versus Maintenance: Patient Selection and Clinical Decision-Making

Segment 3 centers on how clinicians may choose between upfront T-DXd-based therapy and more traditional induction followed by maintenance strategies. Drs. O’Shaughnessy and Rao emphasize that patient populations across trials differ substantially, making cross-trial comparisons challenging. HR status emerges as a key determinant, with ER-positive/HER2-positive patients often benefiting from maintenance strategies that include endocrine therapy and CDK4/6 inhibition, such as PATINA-like approaches.

The panel discusses scenarios where upfront T-DXd may be preferred, including patients with high tumor burden, aggressive disease biology, PIK3CA mutations, or elevated risk for CNS metastases. Data from DESTINY-Breast12 demonstrating robust intracranial activity reinforce the appeal of early T-DXd for patients with existing or high-risk brain metastases. Routine brain imaging is increasingly incorporated into staging for these patients.

Conversely, patients with low-volume, asymptomatic, or oligometastatic disease, particularly those who are HR-positive, may be well-suited for induction therapy followed by maintenance approaches that prioritize quality of life. The ongoing DEMETER trial, evaluating limited cycles of T-DXd followed by antibody maintenance, is highlighted as a potential bridge between these paradigms. The experts discuss the shift toward individualized treatment decisions that integrate disease burden, molecular features, CNS risk, and patient preferences.