ALK rearranged lung cancer: TKI treatment and outcome

Abstract Introduction of tyrosine kinase inhibitors (TKIs) have changed the treatment paradigm and improved the prognosis of oncogenic addicted non-small cell lung cancer patients (NSCLC). Nowadays, for ALK-positive lung cancers three ALK TKI have been approved: crizotinib, alectinib and brigatinib. Both, alectinib and crizotinib are preferred first-line treatment options based on significant improvement in progression free survival and higher intracranial activity compared with crizotinib. However, the new ALK TKIs in first-line setting are being explored such as brigatinib and lorlatinib, which may shift again the treatment paradigm of ALK-positive NSCLC. The mechanisms of acquired resistance to ALK TKI and the most suitable approach upfront as well as at progression, the role of ALK fusion partners for treatment decisions making and how liquid biopsy may improve the knowledge for this disease are current challenges. In this chapter, we summarize the current evidence for the efficacy of the different ALK TKIs in first-line setting and discuss current and future challenges in this disease.