SUMMARY AND RECOMMENDATIONS

SUMMARY AND RECOMMENDATIONS

●The presence of an anaplastic lymphoma kinase (ALK) fusion oncogene defines a molecular subset of non-small cell lung cancer (NSCLC) with distinct clinical and pathologic features. The patients most likely to harbor ALK rearrangement are relatively young, never or light smokers with adenocarcinoma. (See 'Molecular pathogenesis' above and 'Clinicopathologic features' above.)

●Whenever possible, therapy of patients with advanced NSCLC should be individualized based upon the molecular and histologic features of the tumor. If feasible prior to treatment, patients should have tumor tissue assessed for the presence of the ALK fusion oncogene, which is associated with sensitivity to ALK tyrosine kinase inhibitors, as well as other driver mutations such as those seen in the epidermal growth factor receptor (EGFR). (See "Personalized, genotype-directed therapy for advanced non-small cell lung cancer" and 'Chemotherapy versus targeted therapy' above.)

●For patients with advanced or metastatic NSCLC whose tumors contain a characteristic ALK fusion oncogene, we recommend initial treatment with the ALK inhibitor crizotinib rather than chemotherapy (Grade 1B). There currently are insufficient data supporting the use of ceritinib as the initial ALK inhibitor. (See 'Crizotinib' above.)

•Therapy with crizotinib should be continued until there is evidence of progressive disease. In carefully selected patients with an isolated site of recurrence that can be treated with local therapy or those with extremely mild and asymptomatic progression, crizotinib may be continued after initial evidence of progressive disease. (See 'Crizotinib' above.)

•Crizotinib should not be used in patients without ALK rearrangement. In the United States, ALK-positivity must be demonstrated by fluorescence in situ hybridization (FISH) using the US Food and Drug Administration (FDA)-approved test (Vysis Probes) in accordance with the FDA label. In Europe, immunohistochemistry is widely used to detect ALK rearrangement. (See 'Crizotinib' above.)

•Crizotinib is indicated as second-line therapy when progressive disease occurs for patients whose tumor contains the ALK fusion oncogene and initially were treated with chemotherapy. (See 'Crizotinib' above.)

●For ALK-positive patients who develop resistance to crizotinib or who are unable to tolerate crizotinib, we recommend treatment with the second generation ALK inhibitor ceritinib (Grade 1B). (See 'Ceritinib' above.)

●Chemotherapy is an appropriate option for patients who no longer respond to ALK inhibition. (See "Systemic therapy for the initial management of advanced non-small cell lung cancer without a driver mutation" and "Advanced non-small cell lung cancer: Subsequent therapies for previously treated patients".)

●In some cases, chemotherapy is required before the results of molecular testing are available. If the tumor is found to contain the ALK fusion oncogene and patients have an ongoing objective response or stable disease after completing their initial doublet chemotherapy, the authors prefer to switch to crizotinib, although both crizotinib and single-agent maintenance chemotherapy are options. Factors that should be discussed with the patient in defining a treatment plan include the quality of the initial response to chemotherapy and the potential side effects of maintenance therapy. (See "Systemic therapy for the initial management of advanced non-small cell lung cancer without a driver mutation", section on 'Molecular characterization of tumor'.)