A Case of Primary EGFR T790M Mutation in Treatment-Naïve Advanced NSCLC: Clinical and Molecular Implications

Background: De novo (pretreatment) EGFR T790M mutation is a rare molecular finding in non-small cell lung cancer (NSCLC) and has historically been associated with primary resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). Evidence guiding optimal first-line management in this subgroup, particularly in elderly patients, remains limited. Case Presentation: We report a case of an elderly patient with treatment-naïve advanced non-squamous NSCLC harboring a concurrent EGFR exon 19 deletion and de novo EGFR T790M mutation. Given the patient’s age, significant cardiopulmonary comorbidities, and absence of rapidly progressive disease, a multidisciplinary tumor board recommended first-line osimertinib monotherapy. Treatment was well tolerated, with rapid improvement in performance status and no clinically significant adverse events. Serial contrast-enhanced CT restaging demonstrated RECIST 1.1–defined stable disease, without development of new visceral, nodal, cerebral, or osseous metastases. The patient remains on continuous osimertinib therapy with durable disease control at the time of manuscript preparation. Conclusion: Primary EGFR T790M–positive NSCLC can achieve durable disease control with first-line osimertinib, even in advanced age. While combination strategies with chemotherapy may improve survival outcomes in selected patients, treatment decisions in elderly individuals must carefully balance efficacy, toxicity, and quality of life. Chronological age alone should not discourage active targeted treatment when guided by molecular profiling and comprehensive clinical assessment.