Novel ALK Inhibitors in NSCLC With Brain Metastases

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Brain metastases are a significant issue in lung cancer, specifically for patients with ALK-positive non-small cell lung cancer (NSCLC), says Mark A. Socinski, MD. This added concern could be related to the fact that individuals with ALK-positive NSCLC live longer and have more time to develop brain metastases, explains Socinski.

The first generation ALK inhibitor crizotinib is an effective treatment for patients with this subtype of NSCLC; however, it has not demonstrated efficacy in patients with brain metastases. Socinski states that the second-generation ALK inhibitor ceritinib appears to have a greater degree of activity in the central nervous system (CNS) than the first-generation agent crizotinib.

In addition to ceritinib, the second-generation ALK inhibitor alectinib has also demonstrated robust activity in patients with ALK-positive NSCLC following progression on crizotinib, including those with CNS metastases. The FDA approved Ceritinib for patients with ALK-positive NSCLC following crizotinib in 2014. Genentech, the company developing alectinib in the United States, plans to submit data to the FDA for a potential approval for patients with ALK-positive NSCLC sometime this year.