Achievements and future developments of ALK-TKIs in the management of CNS metastases from ALK-positive NSCLC.
Non-small cell lung cancer (NSCLC) represents the paradigm of personalized treatment of human cancer. Several oncogenic druggable alterations have been so far identified, withanaplastic lymphoma kinase(ALK) gene rearrangements being one of the newest and most appealing. Presence ofALKfusions is associated with some particular clinical and pathological features, including a preferential seeding into the central nervous system (CNS). In addition,ALKrearrangements are recognized as the strongest predictor for benefit of anti-ALK therapy. Crizotinib, the first ALK inhibitor (ALK-I) licensed in clinical practice, is the standard of care for newly diagnosed patients. Unfortunately, within the first year of treatment the majority of patients become insensitive to crizotinib, with approximately one third of them developing brain metastases (BMs). Optimal management of BMs is one of the major challenges in treatingALKpositive NSCLC. Several novel and highly CNS penetrant ALK-Is are currently under investigation and available data clearly indicated their ability in controlling intracranial disease.
Medical Oncology Department, ASL Toscana Nord Ovest, Livorno, Italy.
Lorenza
L
Landi
Medical Oncology Department, AUSL Della Romagna, Ravenna, Italy.
Federico
F
Cappuzzo
ALK-inhibitors; Anaplastic lymphoma kinase (ALK); brain metastases (BMs); non-small cell lung cancer (NSCLC)