Background: Multiple single-arm clinical trials have shown promising pathologic complete response (pCR) rates with neoadjuvant ICIs in MIBC. However, ICIs remain costly. We conducted a cost-effectiveness analysis comparing neoadjuvant ICIs with CBC. Methods: We applied a decision analytic simulation model with a health care payer perspective and two-year time horizon to compare neoadjuvant ICIs vs CBC. For the primary analysis we compared pembrolizumab with dose dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC). We performed a secondary analysis with gemcitabine/cisplatin (GC) as CBC and exploratory analyses with atezolizumab or nivolumab/ipilimumab as ICIs (vs both ddMVAC and GC). We input pCR rates from trials (ICIs) or a weighted average of prior studies (CBC) and costs from average sales price. Outcomes of interest included costs, 2-year recurrence-free survival (RFS), and incremental cost-effectiveness ratio (ICER) of cost per 2-year RFS. A threshold analysis estimated a pCR rate or price reduction for ICI to be cost-effective and one-way and probabilistic sensitivity analyses were performed. Results: Results of the cost effectiveness analysis are shown in the table. The incremental cost of pembrolizumab compared with ddMVAC was $8,042 resulting in an incremental improvement of 0.66% in 2-year RFS for an ICER of $1,218,485 per 2-year RFS. A pCR of 71% or a 26% reduction in cost of pembrolizumab would render it more cost-effective with an ICER of $100,000 per 2-year RFS. GC required a 96% pembrolizumab cost reduction to achieve an ICER of $100,000 per 2-year RFS. Atezolizumab appeared to be more cost-effective than ddMVAC, even though the 2yr RFS was 0.66% worse. Conclusions: ICIs were not cost-effective as neoadjuvant therapies, except when atezolizumab was compared with ddMVAC. Pembrolizumab would approach cost-effective thresholds with 26% or 96% reduction in cost when compared to ddMVAC and GC, respectively. Randomized clinical trials, larger sample sizes and longer follow-up are required to better understand the value of ICIs as neoadjuvant treatments.

*Saved with atezolizumab (vs ddMVAC).