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PURPOSE: Several new treatment combinations have been approved in metastatic renal cell carcinoma (mRCC). To determine the optimal therapy on the basis of cost and health outcomes, we performed a cost-effectiveness analysis of approved immunotherapy-tyrosine kinase inhibitor/immunotherapy drug combinations and sunitinib using public payer acquisition costs in the United States. METHODS: We constructed a decision model with a 10-year time horizon. The seven treatment drug strategies included atezolizumab + bevacizumab, avelumab + axitinib, pembrolizumab + axitinib, nivolumab + ipilimumab (NI), nivolumab + cabozantinib, lenvatinib + pembrolizumab, and sunitinib. The effectiveness outcome in our model was quality-adjusted life-years (QALYs) with utility values on the basis of the published literature. Costs included drug acquisition costs and costs for management of grade 3-4 drug-related adverse events. We used a partitioned survival model in which patients with mRCC transitioned between three health states (progression-free, progressive disease, and death) at monthly intervals on the basis of parametric survival function estimated from published survival curves. To determine cost-effectiveness, we constructed incremental cost-effectiveness ratios (ICERs) by dividing the difference in cost by the difference in effectiveness between nondominated treatments. RESULTS: The least expensive treatment was sunitinib ($357,948 US dollars [USD]-$656,100 USD), whereas the most expensive was either lenvatinib + pembrolizumab or pembrolizumab + axitinib ($959,302 USD-$1,403,671 USD). NI yielded the most QALYs (3.6), whereas avelumab + axitinib yielded the least (2.5). NI had an incremental ICER of $297,465 USD-$348,516 USD compared with sunitinib. In sensitivity analyses, this ICER fell below $150,000 USD/QALY if the initial 4-month cost of NI decreased by 22%-38%. CONCLUSION: NI was the most effective combination for mRCC, but at a willingness-to-pay threshold of $150,000 USD/QALY, sunitinib was the most cost-effective approach.

Background: The time frame in which patients can expect functional improvement after open reduction internal fixation (ORIF) of pilon fractures is unclear. The purpose of this study was to determine the trajectory and rate at which patients’ physical function improves up to 2 years postinjury. Methods: The patients studied sustained a unilateral, isolated pilon fractures (AO/OTA 43B/C) and followed at a level 1 trauma center over a 5-year period (2015-2020). Patient-Reported Outcomes Measurement Information Systems (PROMIS) Physical Function (PF) scores from these patients at defined follow-up times of immediately, 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery defined the cohorts and were retrospectively studied. Results: There were 160 patients with PROMIS scores immediately postoperatively, 143 patients at 6 weeks, 146 patients at 12 weeks, 97 at 24 weeks, 84 at 1 year, and 45 at 2 years postoperatively. The average PROMIS PF score was 28 immediately postoperatively, 30 at 6 weeks, 36 at 3 months, 40 at 6 months, 41 at 1 year, and 39 at 2 years. There was a significant difference between PROMIS PF scores between 6 weeks and 3 months ( P < .001), and between 3 and 6 months ( P < .001). Otherwise, no significant differences were detected between consecutive time points. Conclusion: Patients with isolated pilon fractures demonstrate the majority of their improvement in terms of physical function between 6 weeks and 6 months postoperatively. No significant difference was detected in PF scores after 6 months postoperatively up to 2 years. Furthermore, the mean PROMIS PF score of patients 2 years after recovery was approximately 1 SD below the population average. This information is helpful in counseling patients and setting expectations for recovery after pilon fractures. Level of Evidence: Level III, prognostic.

Background Recently several new treatment regimens have been approved for treating metastatic hormone-sensitive prostate cancer (mHSPC), building on androgen deprivation therapy (ADT) alone. These include docetaxel-ADT (DA), Abiraterone Acetate-Prednisone-ADT (AAP), Apalutamide-ADT (AAT), Enzalutamide-ADT (ET), Darolutamide-Docetaxel-ADT (DAD) and Abiraterone- Prednisone-ADT-Docetaxel (AAD). There are no validated predictive biomarkers for choosing a specific regimen. The goal of this study was to conduct a health economic outcome evaluation to determine the optimal treatment from the US public sector (VA). Methods We developed a partitioned survival model in which mHSPC patients transitioned between three health states (progression free, progressive disease to castrate resistance state, and death) at monthly intervals based on Weibull survival model estimated from published Kaplan-Meier curves using a Bayesian network meta-analysis of seven clinical trials (7,208 patients). The effectiveness outcome in our model was quality-adjusted life-years (QALYs). Cost input parameters included initial and subsequent treatment costs and costs for terminal care and for managing grade 3+ drug related adverse events, and were obtained from the Federal Supply Schedule and published literature. Results Average 10-year costs ranged from $34,349 (ADT) to $658,928 (DAD) and mean QALYs ranged from 3.25 (ADT) to 4.57 (ET). Treatment strategies DA, EAD, AAT, and DAD were eliminated due to dominance (ie, they were more costly and less effective than other strategies). Of the remaining strategies, AAP was the most cost-effective strategy at a willingness-to-pay threshold of $100,000/QALY (ICER = $21,247/QALY). Conclusions Our simulation model found AAP to be an optimal first-line treatment for mHSPC from a public (VA) payer perspective.

5081 Background: Recently several new drug treatment regimens have been approved in mHSPC state, building on using androgen deprivation therapy (ADT) alone. These include docetaxel + ADT (DA), Abiraterone Acetate + Prednisone + ADT (AAP), Apalutamide + ADT (AAT), Enzalutamide + ADT (ET), Darolutamide + Docetaxel + ADT (DAD) and AAP + ADT + Docetaxel (AAD). At present, there are no predictive biomarkers for choosing a specific drug regimen over the other. The goal of this study was to conduct an economic evaluation of FDA-approved standard of care drug regimens in the current management of mHSPC state to determine a cost-effective optimal treatment from the US public sector (Veterans Affairs-VA) perspective with a 10-year time horizon. Methods: We developed a partitioned survival model in which mHSPC patients (pts) transitioned between three health states (progression free, progressive disease to castrate resistance state, and death) at monthly intervals based on Weibull survival model estimated from published Kaplan-Meier curves using a network meta-analysis. A Bayesian network meta-analysis of seven randomized clinical trials included 7,208 mHSPC pts. The effectiveness outcome in our model was quality-adjusted life-years (QALYs) with utility values obtained from published literature. Costs in our model included those associated with treatment regimens, subsequent therapies, terminal care, and for managing grade 3-4 drug related adverse events. Costs were obtained from the Federal Supply Schedule and published literature. Incremental cost-effectiveness ratios (ICERs) were calculated for nondominated treatments. Results: Average 10-year costs ranged from $32,697 (ADT) to $649,622 (DAD). Mean QALYs ranged from 3.25 (ADT) to 4.57 (ET). Treatment with DAT, EAD, and DAD were eliminated due to dominance (i.e. they were more costly and less effective than other treatments). AAT was the most cost-effective strategy at a willingness-to-pay threshold of $100,000/QALY (ICER = $70,150/QALY). Results from our analysis for all regimens are shown. Conclusions: Our CEA simulation model found AAT is an optimal cost-effective first-line treatment strategy in mHSPC state from a public (VA) payer perspective. [Table: see text]