Exposure–Response Analyses of Anaplastic Lymphoma Kinase Inhibitors Crizotinib and Alectinib in Non‐Small Cell Lung Cancer Patients

Crizotinib and alectinib are anaplastic lymphoma kinase (ALK)‐inhibitors indicated for the treatment of ALK‐positive metastatic non‐small cell lung cancer (NSCLC). At the currently used fixed doses, interindividual variability in exposure is high. The aim of this study was to investigate whether minimum plasma concentrations (Cmin) of crizotinib and alectinib are related to efficacy and toxicity. An observational study was performed, in which ALK‐positive NSCLC patients who were treated with crizotinib and alectinib and from whom pharmacokinetic samples were collected in routine care, were included in the study. Exposure–response analyses were explored using previously proposed Cmin thresholds of 235 ng/mL for crizotinib and 435 ng/mL for alectinib. Forty‐eight crizotinib and 52 alectinib patients were included. For crizotinib, median progression‐free survival (mPFS) was 5.7 vs. 17.4 months for patients with Cmin