Anti-TROP2 Antibody Drug Conjugates in EGFR-Mutant Non-Small Cell Lung Cancer: Biological Rationale and Clinical Challenges

The emergence of antibody-drug conjugates (ADCs) targeting trophoblast cell-surface antigen 2 (TROP2) represents a potential paradigm shift in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC), a setting historically characterized by limited therapeutic options following progression on EGFR tyrosine kinase inhibitors (TKIs). This review examines the biological rationale and clinical challenges underpinning the development of anti-TROP2 ADCs in EGFR-mutated NSCLC. From a mechanistic standpoint, TROP2 occupies a unique and dynamic role in EGFR-mutated NSCLC, providing strong biological rationale for clinical development of anti-TROP2 ADCs in this population. Three TROP2-directed ADCs are currently in clinical development in this setting. Available clinical data in previously treated EGFR-mutated patients are critically reviewed here, focusing on efficacy, toxicity profiles, clinical challenges and potential future perspectives.