The first cut is the deepest: changing clinical practice for ALK-positive lung cancer

Approximately 4% of non-small-cell lung cancers (NSCLC), mostly adenocarcinomas, harbor oncogenic ALK gene fusions. Patients with such ALK-positive NSCLC tend to be younger, more frequently female and more frequently non-smokers (1,2). Based on superiority to chemotherapy two ALK-tyrosine kinase inhibitors crizotinib (3) and ceritinib (4) were approved for first-line therapy. Hence, both ESMO (5) and CAP (6) guidelines require screening of all NSCLC for ALK fusions, except pure squamous cell carcinomas from heavy smokers. As rapid and cost-effective screening by IHC followed by either by FISH or hybrid capture sequencing has been established, even in patients presenting with very advanced disease and urgent need for therapy first line therapies are possible and effective (7). An illustrative case is shown in Figure 1 and presented in detail previously (7).