Advancing the Needle on the Management of Resectable EGFR-Positive NSCLC: Is Neoadjuvant Osimertinib the Answer?

This article reviews recent efforts to evaluate the use of osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), in the neoadjuvant setting for patients with resectable EGFR-mutant non-small cell lung cancer (NSCLC). While adjuvant osimertinib has shown benefits in delaying recurrence, as shown in the ADAURA trial, its effectiveness as a neoadjuvant monotherapy remains under evaluation. The NORA trial, along with the NEOS trial and a U.S.-based study, showed good tolerability and universal R0 resection rates; however, the objective response rates (ORRs) and low pathologic response were modest, especially in patients with nodal disease. 
 
This editorial discusses how these findings suggest that neoadjuvant osimertinib may be insufficient as monotherapy, particularly when compared to immunotherapy-based combinations used in EGFR-wildtype disease. It calls for future trials to refine patient selection, explore combination strategies (e.g., with chemotherapy), and validate surrogate endpoints such as ctDNA clearance or residual viable tumor. 
 
These insights are highly relevant to the CTSNet community, as it informs surgical planning and the integration of targeted therapies in the evolving landscape of personalized lung cancer treatment.