Looking Ahead in NSCLC Oncodrivers and Targeted Therapies

ASCO 2025 Highlights and Future Directions

ASCO 2025 demonstrated significant advances in lung cancer treatment, particularly in neoadjuvant therapy approaches and biomarker-driven treatment selection. Notable presentations included adaptive trial designs using circulating tumor DNA for treatment escalation decisions, moving beyond static biomarkers toward dynamic assessment tools. The integration of pathologic response assessments and circulating tumor DNA analysis represents the future of personalized treatment approaches in lung cancer management.

Disappointing results emerged in some areas, particularly with patritumab deruxtecan (HER3-DXd) in the HERTHENA-Lung02 study, which failed to meet clinically significance despite statistical significance in progression-free survival (PFS) versus doublet chemotherapy. The withdrawal of FDA applications based on modest improvements highlights the importance of clinically relevant benefits beyond statistical significance. Conversely, promising antibody-drug conjugate data with other agents suggests continued potential in this therapeutic class.

The neoadjuvant space showed promise with osimertinib data in EGFR-positive disease, though major pathologic response rates remained modest compared with immunotherapy approaches. The integration of targeted therapies into perioperative treatment represents an evolving area requiring careful patient selection and treatment sequencing. Future developments will focus on optimizing combination strategies, managing novel toxicities, and ensuring comprehensive biomarker testing reaches all appropriate patients to maximize therapeutic benefits.