The emerging role of antibody-drug conjugates in EGFR-mutant non-small cell lung cancer with acquired resistance to third-generation EGFR tyrosine kinase inhibitors - PubMed
4 hours ago
- #Non-small cell lung cancer
- #EGFR-TKI resistance
- #Antibody-drug conjugates
- Resistance to third-generation EGFR TKIs is a major challenge in EGFR-mutant NSCLC.
- Up to 50% of resistance cases have unknown causes, highlighting the need for non-targeted therapies.
- Antibody-drug conjugates (ADCs) are emerging as a promising treatment option post-EGFR-TKI resistance.
- Trophoblast cell-surface antigen 2 ADCs have been approved by NMPA and FDA for this use.
- ADCs are being explored in clinical trials with both biomarker-selected and unselected patient populations.
- Novel combination strategies, such as chemotherapy plus amivantamab or ivonescimab, are under investigation.
- Toxicity management is a critical aspect of ADC therapy.
- Future directions include optimizing ADC design using AI and multi-omics, novel combination therapies, and personalized toxicity management.
- Efforts are shifting from overcoming resistance to delaying or preventing resistance via patient selection and ctDNA guidance.