Sequential therapy strategies in oncogene-driven NSCLC. (IMAGE)
Caption
Sequential therapy strategies in oncogene-driven NSCLC. This figure illustrates a proposed therapeutic decision-making pathway for patients with NSCLC who develop acquired resistance after initial EGFR-TKI treatment (e.g., osimertinib). After disease progression: • If T790M or C797S resistance mutations are identified, treatment may proceed with next-generation EGFR-TKIs or HER family–directed therapies (e.g., HER3-directed antibody–drug conjugates such as HER3-DXd). • If MET amplification or overexpression is detected, combination therapy with a MET-TKI and HER3-ADC (e.g., HER3-DXd) is suggested. • If no clear resistance mechanism is found, therapeutic options include ADCs, chemotherapy, IO, or brain-penetrant agents if CNS metastases are present, possibly in combination with SABR. All pathways converge on the recommendation for liquid biopsy and NGS to guide molecular profiling and personalized treatment strategies. ADCs, antibody–drug conjugates; CNS, central nervous system; IO, immunotherapy; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; SABR, stereotactic ablative radiotherapy; TKI, tyrosine kinase inhibitor.
Credit
Cancer Biology & Medicine
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