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Anaplastic Lymphoma Kinase Inhibitors for Genetically Rearranged Non-Small Cell Lung Cancer: A Review of the Clinical Effectiveness

Last updated: November 1, 2018
Project Number: RC1036-000
Product Line: Rapid Response
Research Type: Drug
Report Type: Summary with Critical Appraisal
Result type: Report

Question

  1. What is the comparative clinical effectiveness of Anaplastic Lymphoma Kinase inhibitors as first-line therapy for patients with non-resectable Non-Small Cell Lung Cancer?
  2. What is the clinical effectiveness of Anaplastic Lymphoma Kinase inhibitors in patients with non-resectable Non-Small Cell Lung Cancer whose disease has progressed on one or more previous treatments with Anaplastic Lymphoma Kinase (ALK) inhibitors?

Key Message

One health technology assessment report, one network meta-analysis, one systematic review with meta-analyses, and two randomized controlled trials were included in this review. Based on findings from a well-conducted indirect comparison that did not account for first and second-line treatment, alectinib was associated with a longer progression free survival and lower toxicity followed by ceritinib and crizotinib; however, these benefits were not seen in improving objective response rate and disease control rate. Direct comparison using meta-analyses indicated all ALK-inhibitors, regardless of used in patients who were ALK-naive or pretreated, resulted in an improved objective response rate, disease control rate, progression free survival and toxicity; findings did not change with brain metastases. These results, however, were pooled from a mixed group of patients who were ALK-naive and pretreated. Findings from two well-conducted randomized controlled trials showed alectinib to be more clinically efficacious than crizotinib in both ALK-naive and pretreated settings, significantly improving progression free survival, delaying disease progression to the brain, and maintaining a similar or better safety profile.Ceritinib demonstrated clinical benefits in patients pretreated with ALK inhibitors. As reported in a well-conducted meta-analysis, patients refractory to crizotinib had an improvement in objective response rate following ceritinib treatment; however, no improvements were seen in progression free survival or intracranial response.