Cost-utility analysis of EML4-ALK fusion testing followed by treatment with crizotinib in patients with Non-Small Cell Lung Cancer (NSCLC)

Thesis (Master's)--University of Washington, 2015-12Objective NSCLC is the most common type of lung cancer and accounts for about 85% of all lung cancers. Currently a majority of patients with NSCLC are treated with surgical resection and/or cytotoxic drugs. Chemotherapy has resulted in a modest increase (median survival of 8 months with chemotherapy vs median survival of 5.7 months for patients without chemotherapy) in the overall survival of patients. Advances have been made in understanding the molecular mechanisms of lung cancer. The discovery of new biomarkers, driver mutations and signaling pathways in NSCLC has changed the treatment strategy for patients with NSCLC. 'Targeted therapies' or 'personalized medicine' in NSCLC include testing the tumor for the genetic mutations and tailoring the treatment against specific mutations found in the tumor. Success in targeted therapies has been achieved for a small sub-set of NSCLC patients who harbor specific mutations. In 2012, Profile 1007, a phase 3 randomized trial by Pfizer, Inc. demonstrated that crizotinib (Xalkori, Pfizer, Inc.) offers significant improvement in clinical outcomes as a second line therapy for the treatment of EML4-ALK fusion–positive non-small-cell lung cancer (NSCLC). In 2013, the US Food and Drug Administration (FDA) approved crizotinib for the treatment of patients with metastatic NSCLC whose tumors are EML4-ALK fusion positive as detected by the Vysis ALK Break Apart FISH Probe companion diagnostic test (Abbott Molecular). In this paper, we have conducted a cost-utility analysis of EML4-ALK fusion testing of NSCLC patients with the FDA approved companion diagnostic test. Methods We constructed a Markov model to conduct a cost-utility analysis from a health services perspective. We used a lifetime horizon (10 years) in patients with metastatic NSCLC, who had received one prior platinum-based regimen. Utility values and probabilities for the model were obtained from the literature and the drug costs were obtained from 2013 Medicare Drug Fee Schedule. Results EML4-ALK testing with the Vysis ALK Break Apart FISH Probe diagnostic test in a population of metastatic NSCLC patients resulted in an incremental health gain of 0.4055 quality-adjusted life years (QALYs) compared with no molecular testing. Testing for EML4-ALK fusion mutations resulted in an increased cost of USD 56,938. The incremental cost effectiveness ratio (ICER) was USD 140,414 per QALY gained. The major driver of ICER was the low prevalence of ALK rearrangements in the population of NSCLC patients and the cost of crizotinib. Conclusion Overall, EML4-ALK testing with the Vysis ALK Break Apart FISH Probe diagnostic test in a population of metastatic NSCLC patients would not be cost-effective due to high cost of the crizotinib and low prevalence of EML4-ALK mutation in a population of patients with NSCLC