Research Summary:
Traditionally, the gold standard treatment option for patients with cisplatin-eligible clinically localized muscle invasive bladder cancer (MIBC) has been cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with urinary diversion. However, more recently, immune checkpoint inhibitors (ICIs) have been introduced as an alternative treatment option. In the randomized, phase 3 NIAGARA trial, adding durvalumab to neoadjuvant gemcitabine/cisplatin and as adjuvant monotherapy in cisplatin-eligible MIBC was shown to improve event-free and overall survival (OS).1 The results of the NIAGARA trial led to the National Comprehensive Cancer Network recommending neoadjuvant durvalumab with neoadjuvant gemcitabine/cisplatin plus adjuvant durvalumab as a category 1 preferred regimen for cisplatin-eligible MIBC, as well as approval from the United States (US) Food and Drug Administration for this indication. However, before ICIs become established as a standard of care treatment option in patients with MIBC, researchers must understand the potential economic burden and cost-effectiveness of the treatment on healthcare systems and patients with bladder cancer.
To evaluate the cost-effectiveness of perioperative durvalumab with neoadjuvant gemcitabine/cisplatin in patients with cisplatin-eligible localized MIBC, Su et al2 developed a decision-analytic Markov model using safety and efficacy data from the NIAGARA trial. The survival-based decision analysis compared neoadjuvant gemcitabine/cisplatin combined with durvalumab followed by RC and adjuvant durvalumab vs neoadjuvant gemcitabine/cisplatin followed by RC alone; patients in the comparison arm with residual/persistent disease at RC after neoadjuvant chemotherapy were modeled to receive adjuvant nivolumab for up to 1 year. In addition, the model incorporated 3 health states: preprogression, postprogression, and dead. The preprogression state is how patients enter the model. Over time, patients either remain in the preprogression state or transition to the postprogression state if they develop disease progression prior to RC or experience recurrence/metastasis following RC. In the instance of all-cause mortality, patients in either the preprogression or postprogression states permanently transition to the dead state. To characterize state transitions, researchers utilized event-free survival and OS data from the NIAGARA trial. Over a 5-year time horizon using estimations from a US Medicare payer perspective in 28-day model cycles, researchers calculated life years, quality-adjusted life years (QALYs), and direct medical costs.
Compared to treatment with neoadjuvant gemcitabine/cisplatin followed by RC, treatment with neoadjuvant gemcitabine/cisplatin combined with durvalumab followed by RC and adjuvant durvalumab were associated with improvements in life years and QALYs over a 5-year time horizon. Patients treated with neoadjuvant gemcitabine/cisplatin combined with durvalumab followed by RC and adjuvant durvalumab experienced gains in life years of 3.85 vs 3.81 for those who received neoadjuvant gemcitabine/cisplatin followed by RC. Gain in QALYs was 3.05 for the durvalumab arm vs 3.01 for the comparison arm. When researchers alternatively specified a lifetime horizon model for scenario analysis, neoadjuvant gemcitabine/cisplatin combined with durvalumab followed by RC and adjuvant durvalumab was associated with increased improvements in in life years and QALYs, as well as a greater reduction in cumulative costs vs neoadjuvant gemcitabine/cisplatin followed by RC.
Upfront treatment costs were higher with neoadjuvant gemcitabine/cisplatin combined with durvalumab followed by RC and adjuvant durvalumab arm vs neoadjuvant gemcitabine/cisplatin followed by RC alone. However, the durvalumab arm had greater savings in postprogression treatment costs, which resulted in lower total costs ($567,215) vs the comparison arm ($592,368). The durvalumab arm remained dominant over the comparison arm in 3 scenario analyses (assuming no patients in the comparison arm received adjuvant nivolumab; assuming all patients in the comparison arm received adjuvant nivolumab; assuming all patients after disease progression, regardless of prior neoadjuvant or adjuvant therapy, received traditional gemcitabine/cisplatin chemotherapy).
After performing a probabilistic sensitivity analysis, researchers found that the durvalumab arm had a high probability of being cost-effective vs the comparison arm at each willingness-to-pay threshold. Probabilities ranged from 76.8% at a willingness-to-pay threshold of $0/QALY to 78.0% at $250,000/QALY. The durvalumab arm had a 77.3% probability of being cost-effective at the prespecified willingness-to-pay threshold of $100,000/QALY. Additionally, scenario analyses
Overall, for patients in the US with cisplatin-eligible localized MIBC, the addition of perioperative durvalumab to neoadjuvant gemcitabine/cisplatin plus adjuvant durvalumab might be life-extending and cost-effective vs the current standard treatment option of neoadjuvant gemcitabine/cisplatin chemotherapy followed by risk-adapted adjuvant nivolumab. These findings could support the adoption of upfront perioperative durvalumab with neoadjuvant gemcitabine/cisplatin as a new standard treatment option for cisplatin-eligible MIBC.
References
- Powles T, Catto JWF, Galsky MD, et al. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. N Engl J Med. 2024;391:1773–1786.
- Su ZT, Florissi IS, Geller AE, et al. Cost-Effectiveness of perioperative durvalumab with neoadjuvant gemcitabine/cisplatin in muscle-invasive bladder cancer treatment. J Natl Compr Canc Netw. 2026;24(5):172–178.