The Phase 3 DESTINY-Lung04 trial reported improved progression-free survival and response rates with first-line single-agent trastuzumab deruxtecan versus pembrolizumab plus chemotherapy in advanced or metastatic HER2-mutant non-small cell lung cancer. The report noted that overall survival results were confounded by imbalanced subsequent therapies. The readout continues to elevate HER2-targeting antibody-drug conjugates from later-line strategies into earlier treatment settings, where patient selection, dosing schedules, and toxicity management become central for clinical adoption. For the pipeline, the key implication is that developers with ADoC platforms tied to HER2 biology may face faster pathway to standard-of-care if confirmatory OS and safety narratives align across broader biomarker-defined cohorts.