Neurological Involvement in EGFR-mutated Non-small-cell Lung Cancer: A Case Report of Third-generation EGFR-tyrosine Kinase Inhibitor Response

Abstract

Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations benefit from targeted therapy with tyrosine kinase inhibitors (TKIs). Nevertheless, 50-70% of patients will experience progressive disease during TKI therapy, and nearly half will develop resistance mutations such as T790M, for which a third-generation TKI has been developed and proven to be highly effective. One of the most common sites of metastasis in patients with NSCLC is the central nervous system, significantly impacting their and their relatives' quality of life as well as the management of the disease. A patient diagnosed with stage IV lung adenocarcinoma showed progression after 21 months of first-line anti-EGFR therapy and showed clear signs of neurological impairment. The interpretation of cerebral involvement was dubious and difficult: while cerebral spinal fluid cytology seemed to confirm leptomeningeal carcinomatosis, no meningeal nodules or abnormal enhancement was detected on magnetic resonance imaging. Liquid biopsy detected the resistance mutation T790M; hence, therapy was switched to the third-generation TKI osimertinib. The first instrumental re-evaluation revealed a partial response, with a reduction in both lung lesion dimensions and brain alterations. This case shows the effectiveness of osimertinib in treating patients with stage IV NSCLC with central nervous system and bone involvement.