Cost-effectiveness analysis of tumor molecular testing in stage III endometrial cancer (089)

Abstract

<b>Objectives:</b> Treatment of advanced and recurrent endometrial cancer (EC) has traditionally been based on factors, such as histology and stage. Recent studies suggest that tumor molecular profiles may predict treatment outcomes and guide treatment choice. For example, pembrolizumab (PMB) use in patients with mismatch repair deficient (MMRd) tumors versus combined pembrolizumab and lenvatinib (PL) in patients with mismatch repair proficient tumors (MMRp). Furthermore, <i>POLE</i> mutated (<i>POLE</i>mut) tumors demonstrate a favorable prognosis even with minimal treatment. Prospective trials using molecular profiling for treatment assignment are ongoing, but tumor molecular testing (TMT) is costly and time-consuming. We, therefore, sought to evaluate the cost-effectiveness of TMT in stage III EC. <b>Methods:</b> A Markov decision model was created to compare two testing strategies in patients with stage III EC: TMT versus no testing (NT). TMT patients had sequential <i>POLE</i> next-generation sequencing (NGS), mismatch repair (MMR) immunohistochemistry (IHC), and p53 IHC. Adjuvant therapies included radiation (RT) alone for <i>POLE</i>mut and chemoradiation (CTRT) for NT, MMRd, p53 mutated (p53mut), and no specific molecular profile (NSMP) using PORTEC-3 data. All patients received six cycles of carboplatin and paclitaxel (CP) for first recurrence using GOG 209 outcomes. MMRd patients received PMB alone for the second recurrence, whereas all other patients received PL. National database and registry values, literature review, and expert input were used for cost and utility values. A healthcare payer perspective, willingness-to-pay (WTP) threshold of $100,000, and 5-year time horizon were used. Data analysis was done with TreeAge Pro Software 2021. Outcomes were reported in quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses tested model robustness, and a structural sensitivity analysis was performed in which controls underwent MMR IHC alone. <b>Results:</b> Compared to NT, TMT was less costly and more effective. While the model was most sensitive to median overall survival with PL, probability of MMRd status, and cost of lenvatinib, TMT remained cost-saving over all parameters tested. On Monte Carlo analysis, TMT was favored in 79% and 80% of iterations with a WTP of $50,000 and $100,000, respectively. When controls had MMR IHC alone, TMT was no longer cost-effective with an incremental cost of $3100 and incremental effectiveness of 0.017 QALYs, or $184,942/QALY gained. <b>Conclusions:</b> For patients with stage III EC, this model suggests TMT is associated with cost savings compared to NT. However, when compared to MMR IHC alone, a common clinical approach, TMT was no longer a cost-effective strategy at a WTP threshold of $100,000. Further prospective studies are needed to determine the prognostic value of molecular profiles in endometrial cancer. It will be essential to continue assessing the cost-effectiveness of these molecular tests as new data becomes available.