Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Central Nervous System Metastases from Non‐Small Cell Lung Cancer

AbstractCentral nervous system (CNS) metastases are a common complication in patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC), resulting in a poor prognosis and limited treatment options. Treatment of CNS metastases requires a multidisciplinary approach, and the optimal treatment options and sequence of therapies are yet to be established. Many systemic therapies have poor efficacy in the CNS due to the challenges of crossing the blood‐brain barrier (BBB), creating a major unmet need for the development of agents with good BBB‐penetrating biopharmaceutical properties. Although the CNS penetration of first‐ and second‐generation EGFR tyrosine kinase inhibitors (TKIs) is generally low, EGFR‐TKI treatment has been shown to delay time to CNS progression in patients with CNS metastases from EGFR‐mutated disease. However, a major challenge with EGFR‐TKI treatment for patients with NSCLC is the development of acquired resistance, which occurs in most patients treated with a first‐line EGFR‐TKI. Novel EGFR‐TKIs, such as osimertinib, have been specifically designed to address the challenges of acquired resistance and poor BBB permeability and have demonstrated efficacy in the CNS. A rational, iterative drug development process to design agents that could penetrate the BBB could prevent morbidity and mortality associated with CNS disease progression. To ensure a consistent approach to evaluating CNS efficacy, speci...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Lung Cancer, Neuro-Oncology Source Type: research