Next-Generation Strategies in HER2+ mBC: Sequencing Innovations and Clinical Outlooks

Future Directions and Precision Medicine

Future developments in HER2-positive disease focus on addressing remaining gaps, particularly PIK3CA mutations present in one-third of patients at diagnosis. The INAVO122 trial explores alpelisib (a potent PIK3 kinase inhibitor) in hormone receptor–positive, HER2-positive disease, representing precision medicine advancement. Questions remain about integrating these targeted approaches with current treatment paradigms and managing combined toxicities.

Drug development challenges have intensified following impressive DESTINY-Breast09 results, as the progression-free survival bar has been set high for future first-line studies. Companies developing new agents face massive investment requirements to demonstrate superiority over current standards. The success in treatment development paradoxically creates challenges for continued innovation due to the high efficacy benchmarks now established.

Biomarker development represents the next frontier, with investigations into HER2DX and other predictive markers for treatment selection. Circulating tumor DNA integration into clinical decision-making remains under development, with potential applications in treatment continuation decisions and disease monitoring. The ultimate goal involves achieving the “right drug, right time, right patient” precision medicine model while maintaining focus on patient quality of life throughout the treatment journey.