Systemic and Intracranial Efficacy of Osimertinib in L747P-Mutant NSCLC: Case Report

Introduction: L747P mutations occur rarely, with limited preclinical research and case reports suggesting resistance to osimertinib.

Main Concerns Important Clinical Findings Primary Diagnoses Interventions Outcomes: An 84-year-old white male with remote smoking history presented with bilateral pulmonary nodules and multiple subcentimeter enhancing brain lesions 2 years after receiving stereotactic radiation therapy for a left upper lobe lung adenocarcinoma. After two computed tomography-guided biopsies yielded inadequate tissue and cell-free DNA analysis identified no actionable alterations, surgical biopsy results revealed an L747P mutation. Limited case reports and preclinical data suggested that this rare mutation may be resistant to the third-generation EGFR inhibitor osimertinib and recommended use of second-generation EGFR inhibitors. Because the patient had low disease burden and there were concerns on tolerability of second-generation EGFR inhibitors, the patient was initiated on osimertinib. Treatment was well-tolerated and follow-up imaging results revealed thoracic and intracranial response to therapy, which has been sustained 6 months after treatment initiation.

Conclusion: Despite predicted and previously reported resistance, osimertinib may have durable efficacy against rare L747P mutations. Persistent attempts to acquire material for tumor genomic analysis may yield results critically important to clinical management.