High-Risk Populations, Patient Selection, and Advancements in Maintenance Therapy – Insights from Her2Climb05

In this segment, Dr. Sammons and the panel focus on defining high-risk populations in breast cancer and strategies to optimize treatment selection using emerging data from recent clinical trials. The panel underscores the need to identify patients (such as those with positive nodes, residual disease, or aggressive tumor biology) who are most likely to benefit from newer, more intensive therapies. The discussion is substantially informed by the Her2Climb05 trial, which evaluated the role of tucatinib added to maintenance trastuzumab and pertuzumab following induction therapy for HER2-positive metastatic breast cancer. Her2Climb05 demonstrated significant improvement in median progression-free survival—25 months with tucatinib versus 16 months with standard maintenance. Notably, ER-negative patients experienced the greatest benefit (hazard ratio 0.5), highlighting the importance of biomarker-driven patient selection for maintenance strategies.

The panelists elaborate on how Her2Climb05’s results, together with other maintenance and sequencing studies, are reshaping the approach to maintenance therapy: tucatinib-based maintenance is poised to become standard in ER-negative HER2-positive metastatic breast cancer, while other strategies (such as CDK4/6 inhibitors from the Patina trial) may be preferred for ER-positive patients. This risk stratification approach allows clinicians to tailor treatment intensity based on individual patient profiles and trial evidence. The session further discusses how these advances require careful balancing of efficacy, toxicity, and real-world patient characteristics, emphasizing continual re-evaluation as new data emerge.