First-line versus second-line use of pralsetinib in treatment of rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer: a cost-effectiveness analysis

BACKGROUND: The ARROW study demonstrated favorable clinical efficacy and safety of pralsetinib (PRL) in treating rearranged during transfection (RET) fusion positive non-small cell lung cancer (NSCLC) in clinical trials. However, due to the high cost of PRL, evaluating its cost-effective characteristics is crucial. Currently, there has been no cost-effectiveness analysis specifically for PRL. Therefore, the aim of this study was to assess the cost-effectiveness characteristics of using PRL as a first-line therapy versus reserving it until the second-line versus solely relying on chemotherapy from the perspective of payers in the United States. METHODS: A Markov model was developed to evaluate the 3 above mentioned PRL-based treatment strategies. Clinical data from the ARROW trial were incorporated into the model, and costs and utilities values were obtained through previously published literature and public databases, with both being discounted at 3% per year. To ensure the robustness of the model, both probabilistic and univariate sensitivity analyses were performed. The primary endpoints included quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). RESULTS: Compared to chemotherapy, the use of PRL in the first-line therapy resulted in an additional 0.07 QALYs at a cost of $133,561, with an ICER of $1,353,849.65 per QALY. Similarly, when used in the second-line setting, PRL led to an additional 0.09 QALYs at a cost of $92,797, with an ICER of $559,232.70 per QALY. The ICER value in the first-line or in the second-line therapy strategy was higher than the US willingness-to-pay (WTP) threshold of $150,000 per QALY. Univariable sensitivity analyses revealed that the cost of PRL and the utility of progressed disease had the most significant impact on the ICER. To be considered cost-effective at a WTP threshold of $150,000 per QALY, the cost of PRL would need to be reduced by 71.34% in first-line treatment or 84.49% in second-line treatment. CONCLUSIONS: Based on current pricing, neither PRL as first-line nor second-line therapy was found to be cost-effective for patients with RET fusion-positive advanced NSCLC compared to chemotherapy. Reserving PRL until second-line therapy may be a compromise approach to maintaining control over healthcare expenses yet still achieving favorable clinical outcomes.