Monk Bradley J, van Mens Sophie, Hale Oliver, Boer Jennifer, van Hees Frank, Swami Shilpi, Muston Dominic, Tekin Cumhur, Keefe Steve, Monberg Matthew
HonorHealth Research and Innovation Institute, University of Arizona, Creighton University Phoenix, 10510 N 92nd St #200, Scottsdale, AZ, 85258, USA.
Lumanity, Arthur van Schendelstraat 650, 3511 MJ, Utrecht, The Netherlands.
Oncol Ther. 2025 Mar;13(1):85-98. doi: 10.1007/s40487-024-00311-5. Epub 2024 Nov 5.
First-line treatment of persistent, recurrent, or metastatic (advanced) cervical cancer in patients who have a combined positive score (CPS) ≥ 1 with pembrolizumab + chemotherapy versus standard-of-care chemotherapy provides meaningful improvements in overall survival. We conducted a cost-effectiveness analysis from a US payer perspective. A societal perspective scenario was also considered, including productivity gains.
The cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy was assessed using a state-transition model comprising the health states "pre-progression," "post-progression," and "death," with a 1-week cycle length and 50-year time horizon. Patient-level KEYNOTE-826 data informed the efficacy, safety, and health-related quality of life of pembrolizumab + chemotherapy versus chemotherapy at first-line and subsequent treatments. Real-world data were sought to cost subsequent treatments according to US clinical practice. Transition probabilities were derived from parametric survival models fit to time-to-progression, progression-free survival, and post-progression survival patient-level KEYNOTE-826 data. Sensitivity analyses explored the impact on outcomes from variables such as bevacizumab use.
According to the state-transition model, pembrolizumab + chemotherapy extended mean life expectancy versus chemotherapy from 1.8 to 6.7 life-years. The mean gain of 4.9 life-years/patient was mostly caused by pembrolizumab delaying progression. Total discounted quality-adjusted life-years (QALY) were 5.0 and 1.3 per patient for pembrolizumab + chemotherapy and chemotherapy, respectively (mean gain: 3.7 QALY/patient). Pembrolizumab + chemotherapy had comparable safety outcomes to chemotherapy alone. Total costs incurred were US $320,247 (pembrolizumab + chemotherapy) versus US $105,446 (chemotherapy; mean incremental costs: US $214,801/patient). The incremental cost-effectiveness ratio of pembrolizumab + chemotherapy versus chemotherapy was US $58,446/QALY. Sensitivity analyses showed results were insensitive to bevacizumab use. Including productivity gains led to an incremental cost-effectiveness ratio of US $58,385 per QALY.
Our model-based analysis suggests that first-line treatment of pembrolizumab + chemotherapy in advanced cervical cancer with a CPS ≥ 1 offers a substantial clinical benefit over standard-of-care chemotherapy alone and is cost-effective at a willingness-to-pay threshold of US $150,000. The approximate doubling of life-years and QALYs associated with pembrolizumab + chemotherapy represents a step improvement in the treatment of advanced cervical cancer.
ClinicalTrials.gov Identification Number: NCT03635567.
对于联合阳性评分(CPS)≥1的持续性、复发性或转移性(晚期)宫颈癌患者,帕博利珠单抗联合化疗与标准护理化疗相比,可显著提高总生存期。我们从美国医保支付方的角度进行了成本效益分析。同时也考虑了包括生产力提高在内的社会视角情况。
使用一个状态转换模型评估帕博利珠单抗联合化疗与化疗的成本效益,该模型包括“进展前”“进展后”和“死亡”三种健康状态,周期长度为1周,时间跨度为50年。患者层面的KEYNOTE-826数据为一线及后续治疗中帕博利珠单抗联合化疗与化疗的疗效、安全性及健康相关生活质量提供了依据。根据美国临床实践,寻求真实世界数据以估算后续治疗的成本。转移概率来自根据疾病进展时间、无进展生存期和进展后生存期患者层面的KEYNOTE-826数据拟合的参数生存模型。敏感性分析探讨了诸如使用贝伐单抗等变量对结果的影响。
根据状态转换模型,与化疗相比,帕博利珠单抗联合化疗将平均预期寿命从1.8年延长至6.7年。每位患者平均延长4.9年主要是由于帕博利珠单抗延缓了疾病进展。帕博利珠单抗联合化疗和化疗的每位患者总贴现质量调整生命年(QALY)分别为5.0和1.3(平均增加:3.7 QALY/患者)。帕博利珠单抗联合化疗的安全性结果与单纯化疗相当。所产生的总成本为320,247美元(帕博利珠单抗联合化疗)与105,446美元(化疗;平均增量成本:214,801美元/患者)。帕博利珠单抗联合化疗与化疗相比的增量成本效益比为58,446美元/QALY。敏感性分析表明结果对贝伐单抗的使用不敏感。纳入生产力提高因素后,增量成本效益比为每QALY 58,385美元。
我们基于模型的分析表明,对于CPS≥1的晚期宫颈癌,一线使用帕博利珠单抗联合化疗比单纯标准护理化疗具有显著的临床益处,并且在支付意愿阈值为150,000美元时具有成本效益。与帕博利珠单抗联合化疗相关的生命年和QALY大约翻倍,代表了晚期宫颈癌治疗的显著进步。
ClinicalTrials.gov识别号:NCT03635567。