OBJECTIVES: To assess the cost-utility of crizotinib, ceritinib, and alectinib as first-line treatments in patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) from a US societal perspective.

METHODS: A Markov model with three health states (stable disease, disease progression, and death) was developed. Transition probabilities were calculated from key clinical trials (crizotinib: NCT00932893, ceritinib: NCT01828099, alectinib: NCT02075840). The time horizon in the model was 5 years with a 3-week cycle length. Physician visit and procedure costs were derived from the Medicare physician-fee-schedule. Drug acquisition costs were based on prices from the Veteran Affairs Federal Supply Schedule. Costs of adverse events, caregiver's costs, and utility values were obtained from relevant literature. A 3% annual discount rate was applied and all costs were adjusted to 2017 US dollars. The primary outcome was incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the model results.

RESULTS: Compared with crizotinib, the ICERs for ceritinib and alectinib were $357,708 per quality adjusted life-year (QALY) gained and $333,840 per QALY gained, respectively. The alectinib vs ceritinib yielded a gain of 0.41 QALYs and additional $132,746 costs, resulting in the ICER of $325,009 per QALY gained. In the one-way sensitivity analyses, the model results were most sensitive to median overall survival, progression-free survival, and utility values. The results were robust to variations in other parameters. For ceritinib and alectinib to be cost-effective at standard thresholds, their price would have to drop by at least 38%.

CONCLUSIONS: Compared with crizotinib, ceritinib and alectinib both improved total QALYs. However, using a U.S. willingness-to-pay threshold of $150,000/QALY, ceritinib and alectinib were not cost-effective compared with crizotinib for the first-line treatments of ALK positive metastatic NSCLC.