Cost-effectiveness of Perioperative Durvalumab Plus Platinum-based Chemotherapy in Muscle Invasive Bladder Cancer - Expert Commentary
The researchers constructed a Markov model from the payer's perspective, incorporating clinical data derived from the NIAGARA trial. The model compared two treatment strategies over a 5-year time horizon with 3-month cycles. The prior standard of care (SoC) comprised neoadjuvant chemotherapy with gemcitabine (1000 mg/m² on days 1 and 8) and cisplatin (70 mg/m² on day 1) administered for three to four cycles, followed by radical cystectomy. The intervention arm included the same neoadjuvant chemotherapy regimen in combination with four cycles of durvalumab (1500 mg), followed by postoperative adjuvant immunotherapy with durvalumab (1500 mg) for up to eight cycles. A Monte Carlo simulation with 1000 iterations was employed to determine the most cost-effective treatment strategy.
The analysis revealed that the average cost associated with the SoC was €113,224, whereas the combination of durvalumab with gemcitabine/cisplatin resulted in an average cost of €126,386, leading to incremental costs of €13,162. The quality-adjusted life years (QALYs) gained were 3.16 for the SoC and 3.37 for the intervention, corresponding to an incremental effectiveness of 0.21 QALYs. The resulting incremental cost-effectiveness ratio (ICER) for the combination therapy was €61,006 per QALY. At a willingness-to-pay (WTP) threshold of €50,000, gemcitabine/cisplatin alone was cost-effective in 59.4% of simulations. However, at a WTP threshold of €100,000, the addition of durvalumab to gemcitabine/cisplatin emerged as the preferred treatment option, with a 76.5% probability of being cost-effective (p = 0.765). This probability further increased to 94.2% at a WTP threshold of €150,000.
The sensitivity analysis identified that model outcomes were most sensitive to the costs of novel medications, particularly enfortumab vedotin plus pembrolizumab (EV + P) as treatment in the metastatic setting, and durvalumab in the intervention arm. A cost reduction of approximately 17% for EV + P would render the intervention arm no longer cost-effective at a WTP threshold of €100,000. Conversely, increasing the cost of durvalumab by 10% per Markov cycle would also result in the intervention arm falling outside the cost-effectiveness threshold. A significant proportion of the costs observed in the simulations was attributable to expenses associated with subsequent therapies administered in the metastatic disease setting.
The study demonstrated that the incorporation of durvalumab into the perioperative treatment regimen constitutes a cost-effective strategy, primarily due to its potential to reduce the need for high-cost subsequent therapies in a proportion of patients.
Importantly, the NIAGARA trial showed that Event-Free Survival at 24 months was approximately 68% in the intervention arm compared to 60% in the control arm, and even this modest difference had a significant impact on downstream costs related to expensive metastatic disease management. The analysis was subject to several limitations, including the relatively short follow-up period of the NIAGARA trial, modeling of subsequent treatment pathways according to current guidelines rather than actual trial data, and analysis conducted specifically within the German healthcare system framework. These findings suggest that preventing progression to metastatic disease through perioperative durvalumab treatment is both clinically and economically valuable reducing the need for expensive subsequent therapies.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
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