OBJECTIVES: : To assess the cost-effectiveness of ceritinib versus  alternatives in patients who discontinue  treatment with crizotinib in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) from a Canadian healthcare perspective. METHODS: A partitioned survival model with three health states (progression-free, progressive, and death) was developed to compare ceritinib versus other alternatives in patients with ALK+ NSCLC who were previously treated with an ALK inhibitor. Comparators were chosen based on reported utilization from a retrospective Canadian chart study; comparators were pemetrexed, best-supportive care (BSC) and historical control. Progression-free survival and overall survival for ceritinib were estimated using  data from reported single-arm clinical trials (ASCEND-1(NCT01283516) and ASCEND-2(NCT01685060)). Survival data for comparators were obtained from published clinical trials in general NSCLC population and from a Canadian retrospective chart study in ALK+ patients treated with crizotinib. Parametric models were used to extrapolate outcomes beyond trial period. Drug acquisition, administration, resource use and adverse event (AE) costs were obtained from public databases. Utilities for health states and disutilities for AEs based on EQ-5D were derived from literature. Incremental costs per quality-adjusted life year (QALY) gained were estimated. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Over 4 years, ceritinib was associated with  0.86 QALYs and total direct costs of $89,740 for post-ALK population. The incremental cost per QALY was $149,117 comparing ceritinib vs. BSC, $80,100 vs.  pemetrexed, and 104,436 vs.  historical controls. Additional scenarios included comparison to docetaxel with an ICER/QALY of $149,780 and utility scores reported from PROFILE 1007, with a reported ICER/QALY ranging from $62,543  vs. pemetrexed to $119,735 vs. BSC. Sensitivity analysis results were consistent with the base-case findings. CONCLUSIONS: Based on the willingness-to-pay threshold for end-of-life cancer drugs, ceritinib may be considered as a cost-effective option compared with other alternatives in patients who have progressed or are intolerant to crizotinib.