Intracranial activity of crizotinib: something to rely on?

Central nervous system (CNS) metastases remain a significant problem in the management of patients with ALK-rearranged non-small cell lung cancer (NSCLC). The frequency of CNS involvement in ALK-positive tumors is extremely high; it approaches 25% in treatment naïve patients (1) and rises to 50% in patients treated with crizotinib (2,3). Crizotinib was previously reported to have only minor intracranial activity (4), with poor CNS penetration suggested as the underlying mechanism (5).