In the phase 3 trial OptiTROP-Lung04, 376 patients with EGFR-mutated (ex19del/L858R) advanced non-small cell lung cancer progressing after EGFR-TKIs were randomized to the antibody-drug conjugate (ADC) sacituzumab tirumotecan versus standard pemetrexed + platinum. Recall sacituzumab is an anti-Trop-2 monoclonal antibody and tirumotecan is another topoisomerase I inhibitor. Here the ADC halved the risk of progression achieving a median progression-free survival of 8 versus 4 months with chemo. Most notably, overall survival was also significantly improved (HR 0.60), and benefit persisted despite 20% progressing post-chemo crossing over to ADC. Stomatitis (64%) was the signature side effect of the ADC, typically resolving with dose reductions rather than discontinuation. | Fang, N Engl J Med 2026
