Research Summary:
Muscle invasive bladder cancer (MIBC) is an aggressive subtype of bladder cancer that invades the musculature of the bladder wall. Current standard treatment involves neoadjuvant chemotherapy followed by radical cystectomy, but MIBC carries a high risk of recurrence, with about half of patients experiencing recurrence within 3 years, highlighting the need for more effective perioperative treatment strategies. Immune checkpoint inhibitors have been increasingly integrated into neoadjuvant and adjuvant treatment, where they enhance antitumor immunity and can improve a patient’s immune response. In the phase 3 NIAGARA trial, durvalumab, a human immunoglobulin G1 monoclonal antibody targeting programmed death ligand 1, improved event-free survival (EFS) and overall survival (OS) when added to gemcitabine–cisplatin (GC) chemotherapy, with a 24-month EFS of 67.8% vs 59.8% and OS of 82.2% vs 75.2% when compared to chemotherapy alone. As bladder cancer is among the most expensive cancers to manage in the United States (US), You et al1 evaluated the cost effectiveness of perioperative durvalumab plus neoadjuvant chemotherapy vs neoadjuvant chemotherapy alone for operable MIBC.
The authors conducted a model-based pharmacoeconomic evaluation using efficacy and safety data from the NIAGARA trial, which enrolled adults aged at least 18 years of age with operable MIBC who were eligible for cisplatin-based neoadjuvant chemotherapy and radical cystectomy. Patients were randomized 1:1 to receive either 4 cycles of durvalumab plus gemcitabine–cisplatin (DGC) followed by radical cystectomy and up to 8 cycles of adjuvant durvalumab, or 4 cycles of GC alone followed by radical cystectomy. In the absence of detailed reporting of postrecurrence therapies in the NIAGARA trial, the model assumed that patients with recurrence within 1 year after surgery received pembrolizumab, whereas those with later recurrence received GC, and patients not receiving these regimens received best supportive care. The analysis adopted a US healthcare payer perspective and included only direct medical costs, including drugs, administration, follow-up imaging, laboratory tests, office visits, management of grade 3 or higher adverse events (AEs), best supportive care, and end-of-life care.
The primary outcomes of interest were total costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). A willingness-to-pay (WTP) threshold of $150,000 per QALY was applied, consistent with World Health Organization guidelines. Sensitivity analyses used gamma distributions for costs and beta distributions for transition probabilities, health utilities, and AEs. A probabilistic sensitivity analysis used Monte Carlo simulations to generate cost-effectiveness acceptability curves and scatter plots. Scenario analyses varied model duration (10 vs 5 years), discount rates, and proportion of patients receiving subsequent treatment after disease progression (100%, 80%, or 50%).
In the base-case 10-year analysis, total costs were $227,802.40 for the DGC group and $164,048.73 for the GC group, yielding an incremental change of $63,753.67. For the DGC and GC groups, total life-years were 7.23 and 6.84, respectively, and total QALYs were 5.86 and 5.18, respectively, yielding an incremental gain of 0.68 QALY. The resulting ICER was $93,693.79 per QALY, which was below the $150,000 per QALY WTP threshold, suggesting that durvalumab plus chemotherapy is a cost-effective treatment strategy. The incremental cost was mainly attributable to durvalumab drug acquisition, whereas AE management costs were lower with durvalumab plus chemotherapy because of a lower incidence of severe toxicities. Follow-up and end-of-life care costs were similar between the 2 strategies.
Sensitivity analyses showed that the ICER was most sensitive to the cost of durvalumab and the discount rate; variations in these parameters produced the widest range of ICER values but did not push the ICER above the WTP threshold. Probabilistic sensitivity analysis showed that durvalumab plus chemotherapy consistently incurred higher costs but delivered additional QALYs. The cost-effectiveness acceptability curve showed that at a WTP threshold of $150,000 per QALY, DGC had a 91.95% probability of being cost effective compared to GC. Scenario analyses yielded ICERs that were generally consistent with cost effectiveness over longer durations. When the model horizon was truncated to 5 years, the ICER increased to $359,493.07 per QALY, reflecting high upfront costs with less time to accrue survival benefit. When utilities or costs were discounted separately, ICERs decreased to $74,625.79 and $79,722.90 per QALY, respectively, and in the absence of discounting, the ICER was $63,498.17 per QALY. When only 80% or 50% of patients were assumed to receive subsequent treatment after recurrence, ICERs were $114,377.03 and $145,401.87 per QALY, respectively, both remaining below the $150,000 per QALY threshold.
Perioperative durvalumab combined with neoadjuvant gemcitabine–cisplatin treatment was shown to increase QALYs and life-years compared to neoadjuvant chemotherapy alone for patients with operable MIBC. Across sensitivity and scenario analyses, durvalumab plus chemotherapy remained economically favorable in most settings, supporting its classification as a cost-effective perioperative strategy for patients with MIBC.
References
- You C, Zhang J, Lei J, et al. Cost-effectiveness of perioperative durvalumab plus neoadjuvant chemotherapy for muscle invasive bladder cancer in the United States. Ther Adv Med Oncol. 2025;17:17588359251357519.