Crizotinib for ALK rearrangement-positive non-small cell lung cancer patients with central nervous system metastasis

Patients with central nervous system (CNS) metastases in general experience have a deterioration in performance status and a limited survival time (1). CNS metastasis of non-small cell lung cancer (NSCLC) has been the subject of renewed interest of late given that small-molecule tyrosine kinase inhibitors (TKIs), such as those that target activated forms of the epidermal growth factor receptor (EGFR), have the potential to improve local tumor control in molecularly selected individuals. Given that the concentration of EGFR-TKIs is much lower in cerebrospinal fluid (CSF) than in plasma, however, frequent isolated CNS metastasis, without other systemic progression, has been detected in patients with advanced NSCLC who show a response to these drugs (2). Similar concerns have also been raised for patients with NSCLC positive for the EML4-ALK fusion gene treated with the anaplastic lymphoma kinase (ALK)-targeted TKI crizotinib.