This review (second in a Lancet Respiratory Medicine series) summarizes the current landscape of biomarker-matched targeted therapies in advanced NSCLC, covering established drivers (EGFR, ALK, ROS1, KRAS, BRAF, RET, HER2, MET, NTRK) and emerging targets (NRG1 fusions, MTAP loss, SMARCA4 deficiency), including newer TKI generations, bispecific antibodies, and antibody-drug conjugates (ADCs).
Across established drivers, next-generation TKIs, bispecific antibodies (e.g., amivantamab–lazertinib), and ADCs (e.g., trastuzumab deruxtecan, sacituzumab tirumotecan) have improved response durability, intracranial disease control, and in some settings overall survival; however, acquired resistance, tumor heterogeneity, lineage plasticity, and off-target escape remain key barriers to durable benefit.
Full text was not accessible — the summary is based solely on the abstract and reference list, which limits extraction of specific outcome data, patient numbers, and granular trial results. This is a narrative review series paper, not a primary study, so no single efficacy estimate applies.
For advanced NSCLC, comprehensive upfront molecular profiling and timely biomarker testing are essential, as an expanding number of drivers now have matched therapies that outperform chemotherapy. Repeat tissue biopsy or circulating-tumor DNA testing at progression is increasingly important to identify actionable resistance mechanisms and guide next-line therapy.
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