New Treatment Options for ALK-Rearranged Non-Small Cell Lung Cancer.

摘要: ALK rearrangements are present in 3–5 % of patients with non-small cell lung cancer (NSCLC) and after epidermal growth factor receptor (EGFR) mutations represent the second molecular target NSCLC to be validated through phase III clinical trials. The PROFILE 1014 international multicentre trial demonstrated superiority crizotinib over standard chemotherapy, establishing as first-line therapy for advanced ALK-positive indicating requirement testing guide selection optimal non-squamous NSCLC. Despite impressive durable responses, progression on treatment reflecting development acquired resistance is inevitable. There several mechanisms including kinase mutation or copy number gain, activation bypass pathways potentially pharmacokinetic failure (most commonly CNS). A broad array newer generation inhibitors that appear effective crizotinib-resistant setting intracranial progression. These agents, ceritinib alectinib, have a higher potency against than crizotinib, activity confer improved CNS penetration. While selected patients, continued local ablative treatments oligo-progressive systemic disease may an option, many use compound will effective. First-line potential advantages sequential crizotinib; however, sequence has not been determined being explored ongoing studies.