Courtney P Travis, Venkat Puja S, Shih Ya-Chen Tina, Chang Albert J, Lee Alan, Steinberg Michael L, Raldow Ann C
Department of Radiation Oncology, University of California, Los Angeles.
JAMA Netw Open. 2025 Mar 3;8(3):e250033. doi: 10.1001/jamanetworkopen.2025.0033.
The KEYNOTE-A18 trial demonstrated that adding concurrent and adjuvant pembrolizumab to chemoradiotherapy and brachytherapy significantly improved survival in patients with newly diagnosed, locally advanced cervical cancer. However, considering the annual global incidence of 660 000 cases of cervical cancer, including 13 820 in the US in 2024, incorporating this regimen into the standard of care could have substantial health care economic implications for both patients and the health care system.
To determine the cost-effectiveness of adding pembrolizumab to the first-line treatment of newly diagnosed, locally advanced cervical cancer.
DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation created a Markov model simulating 50-year outcomes to evaluate cost-effectiveness from the payer perspective for patients receiving either pembrolizumab or placebo in addition to chemoradiotherapy plus brachytherapy. Probabilities, including disease progression, survival, and treatment-related toxic effects, were derived from KEYNOTE-A18 clinical trial data in patients with newly diagnosed, locally advanced cervical cancer. Costs and health utilities were obtained from published literature; 1-way, 3-way, and probabilistic sensitivity analyses were used to assess model uncertainty. Data analyses were conducted from April to November 2024.
Pembrolizumab.
Costs, measured in 2024 US dollars, and effectiveness, measured in quality-adjusted life-years (QALYs) were used to calculate an incremental cost-effectiveness ratio (ICER). A willingness-to-pay threshold of $100 000 per QALY was chosen, below which pembrolizumab would be considered cost-effective.
KEYNOTE-A18 enrolled 1060 patients (529 in pembrolizumab group, 531 in placebo group). The median age was 50 years. Pembrolizumab increased costs by $257 000 and effectiveness by 1.40 QALYs, yielding an incremental cost-effectiveness ratio of $183 400 per QALY. The addition of pembrolizumab became cost-effective if its monthly cost was decreased from $16 990 to $9190 (a 45.6% reduction) or its maximum duration of 24 months was decreased to 10 months. The model was insensitive to assumptions about treatment-related toxic effects, progression-free survival, and overall survival. Probabilistic sensitivity analysis indicated that at a willingness-to-pay threshold of $100 000 per QALY, the addition of pembrolizumab was cost-effective 37.3% of the time.
In this economic evaluation of adding concurrent and adjuvant pembrolizumab to first-line treatment of newly diagnosed, locally advanced cervical cancer, this regimen was not cost-effective at current prices despite data demonstrating improved survival with this regimen.
KEYNOTE - A18试验表明，在同步放化疗及近距离放疗基础上联合使用帕博利珠单抗进行辅助治疗，可显著提高新诊断的局部晚期宫颈癌患者的生存率。然而，考虑到全球每年宫颈癌的发病率为66万例，其中2024年美国有13820例，将该方案纳入标准治疗可能会对患者和医疗保健系统产生重大的医疗保健经济影响。
确定在新诊断的局部晚期宫颈癌一线治疗中添加帕博利珠单抗的成本效益。
设计、设置和参与者：这项经济评估创建了一个马尔可夫模型，模拟50年的结果，从支付方的角度评估在同步放化疗加近距离放疗基础上接受帕博利珠单抗或安慰剂治疗的患者的成本效益。包括疾病进展、生存和治疗相关毒性作用的概率来自KEYNOTE - A18临床试验中确诊的局部晚期宫颈癌患者的数据。成本和健康效用数据来自已发表的文献；采用单因素、三因素和概率敏感性分析来评估模型的不确定性。数据分析于2024年4月至11月进行。
帕博利珠单抗。
以2024年美元计算的成本，以及以质量调整生命年（QALY）衡量的有效性，用于计算增量成本效益比（ICER）。选择了每QALY 10万美元的支付意愿阈值，低于该阈值，帕博利珠单抗将被视为具有成本效益。
KEYNOTE - A18试验纳入了1060例患者（帕博利珠单抗组529例，安慰剂组531例）。中位年龄为50岁。帕博利珠单抗使成本增加了25.7万美元，有效性增加了1.40个QALY，产生的增量成本效益比为每QALY 18.34万美元。如果帕博利珠单抗的月费用从16990美元降至9190美元（降低45.6%）或其最长使用时长从24个月降至10个月，添加帕博利珠单抗就会变得具有成本效益。该模型对有关治疗相关毒性作用、无进展生存期和总生存期的假设不敏感。概率敏感性分析表明，在每QALY 10万美元的支付意愿阈值下，添加帕博利珠单抗在37.3%的时间内具有成本效益。
在这项关于在新诊断的局部晚期宫颈癌一线治疗中添加同步及辅助帕博利珠单抗的经济评估中，尽管数据表明该方案可提高生存率，但按当前价格计算，该方案不具有成本效益。
