Ceritinib in second and further lines of therapy in advanced ALK mutant adenocarcinoma

Crizotinib is the first approved ALK inhibitor in advanced, ALK-positive non-small cell lung cancer (NSCLC). When administered in first line, median progression-free survival (mPFS) was 10.9 months (ms) with crizotinib versus 7.0 ms with best cytostatic chemotherapy. Overall response rate was 74% with crizotinib versus 45% with chemotherapy (1). In second line mPFS of 7.7 ms has been reported with crizotinib versus 3.0 ms with chemotherapy (2). Thus, crizotinib has proved to be more effective than chemotherapy in advanced, ALK-positive NSCLC. But there are limitations: (I) majority of patients develop resistance to this drug within 1–2 years from initiation of treatment and (II) crizotinib has poor activity against central nervous system (CNS) metastasis of ALK-positive NSCLC. CNS concentration of crizotinib is three orders of magnitude less than the plasma concentration (3). While crizotinib treatment has been documented to provide median overall survival (OS) as long as 49.5 ms, within this same patient population the median intracranial progression-free interval was only 11.9 ms (4). Crizotinib is relatively weak against CNS metastasis formation or progression, therefore close CNS observation seems to be critical during crizotinib treatment