OBJECTIVES: Identifying cancer patients who may benefit from targeted therapies is essential for treatment decisions. Due to the large number of potential oncogenic drivers in advanced non-small cell lung cancer (NSCLC), next-generation sequencing (NGS) is guideline-recommended for identifying actionable targets to inform treatment decisions. Multiple testing options incorporating DNA and/or RNA sequencing are available. Given the potential for improved detection of actionable fusions using RNA sequencing, we examined the costs associated with these testing options.

METHODS: A Microsoft Excel-based model was developed to evaluate patients diagnosed with advanced/metastatic NSCLC. Treatment pathways were based on NCCN guidelines and expert opinion. Economic inputs were estimated for one year based on published literature, including cost of NGS testing based on a generic CPT code, treatment costs, and productivity losses. A range of 2.5-14% was considered for the rate of fusions detected by RNA but not DNA sequencing. Outputs included the number of actionable fusions identified and costs. Results were estimated for patients receiving NGS testing with DNA-only sequencing with/without reflex RNA testing and DNA+RNA sequencing.

RESULTS: Based on the model, tests that include RNA sequencing increased the number of fusions identified compared with DNA sequencing alone without reflex RNA testing. Use of reflex RNA testing increased costs per NSCLC patient compared with upfront DNA+RNA sequencing, with cost savings ranging from $349 at the 2.5% level to $741 at the 14% level of additive detection.

CONCLUSIONS: In advanced NSCLC, NGS tests that include DNA and RNA sequencing identify those eligible for targeted therapies more efficiently, depending on the additive detection rate of fusions by RNA-sequencing. Upfront DNA+RNA testing also reduces both costs and turn-around-time compared with initial DNA sequencing followed by reflex RNA sequencing. Further investigations into the advantages of RNA sequencing are warranted.