晚期非小细胞肺癌治疗中潜在预测性生物标志物的早期健康技术评估

IF 2 Q2 ECONOMICS
PharmacoEconomics Open Pub Date : 2025-05-01 Epub Date: 2025-01-28 DOI:10.1007/s41669-025-00557-3
Leila-Sophie Otten, Alessandra I G Buma, Berber Piet, Rob Ter Heine, Michel M van den Heuvel, Valesca P Retèl
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引用次数: 0

摘要

目的:含免疫检查点抑制剂(ICI)的治疗目前是所有无靶向驱动突变的晚期非小细胞肺癌(NSCLC)患者的一线治疗。然而,只有30-45%的患者在治疗开始后12个月内无进展。目前正在研究各种生物标记物,以节省对无反应者进行昂贵且可能有害的治疗。我们评估了荷兰晚期NSCLC患者在含派姆单抗治疗中,与标准护理(例如,未实施生物标志物)相比,实施一种假设的预测性生物标志物对含ici治疗反应的成本效益。材料和方法:根据患者的肿瘤程序性细胞死亡配体-1 (PD-L1)表达和组织学,使用马尔可夫模型对三种一线含派姆单抗治疗的基于标准护理和基于预测生物标志物的策略进行比较。采用了荷兰医疗保健系统的观点。假设在识别应答者时,应答者的工作特征面积在1.0曲线下,在基于预测-生物标志物的策略中为无应答者提供替代治疗。参数和假设基于来自调查的真实数据、使用目标搜索的文献、专家意见和注册表。结果包括预测生物标志物和基于标准护理策略之间的成本、生存(生命年(LYs))和健康相关生活质量(QoL)校正生存(QALYs)的差异。结果:在派姆单抗-卡铂-紫杉醇治疗中实施预测性生物标志物导致平均生存期减少24天(- 0.067个生命周期)(生活质量纠正18天(- 0.049个生命周期)),与标准护理相比节省成本22,606欧元。Pembrolizumab单药治疗和Pembrolizumab -培美曲塞-铂治疗分别显示生存期减少4.5和3.9个月(生活质量校正3.6和2.8个月),成本节省24,345欧元和28,456欧元。敏感性分析证实了持续的成本节约和生存率降低。观察到的生存损失主要是由于在每个含派姆单抗的治疗方案中,基于预测生物标志物的策略可用于无反应的替代一线治疗方案的生存率较低。派姆单抗-卡铂-紫杉醇治疗在某些条件下也显示出与QoL和生存估计相关的生存获益。结论:我们的研究强调了在晚期非小细胞肺癌中谨慎实施ici治疗的重要性,在不影响生存的情况下平衡成本降低和副作用。在派姆单抗-卡铂-紫杉醇治疗方案中,生存损失可以忽略不计。未来的研究应定义可接受的权衡和取消实施的阈值,考虑替代治疗的生存和应答者分类等因素,以指导预测性生物标志物的实施和优化卫生资源分配。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Very Early Health Technology Assessment for Potential Predictive Biomarkers in the Treatment of Advanced Non-Small Cell Lung Cancer.

Objectives: Immune checkpoint inhibitor (ICI)-containing treatment is currently prescribed as first-line treatment for all patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, only 30-45% of patients show no progression within 12 months after treatment start. Various biomarkers are being studied to save costly and potentially harmful treatment in non-responders. We evaluated the cost-effectiveness of implementing a hypothetical predictive biomarker for ICI-containing treatment response compared with standard of care (e.g., no implemented biomarker) for pembrolizumab-containing treatment in patients with advanced NSCLC in the Netherlands.

Materials and methods: Standard-of-care-based and predictive-biomarker-based strategies were compared using Markov models for three first-line pembrolizumab-containing treatments depending on a patient's tumor programmed cell death ligand-1 (PD-L1) expression and histology. A Dutch healthcare system perspective was adopted. Assuming a receiver operating characteristic-area under the curve of 1.0 in identifying responders, alternative treatments were offered for non-responders in the predictive-biomarker-based strategy. Parameters and assumptions were based on real-world data from surveys, literature using a targeted search, expert opinion, and registries. Outcomes included differences in costs, survival (life years (LYs)), and survival corrected for health-related quality of life (QoL) quality-adjusted life-years (QALYs) between the predictive-biomarker- and standard-of-care-based strategy.

Results: Implementing a predictive biomarker in pembrolizumab-carboplatin-paclitaxel treatment led to a mean survival reduction of 24 days (- 0.067 LYs) (18 days corrected for QoL (- 0.049 QALYs)), with cost savings of €22,606 compared with standard of care. Pembrolizumab monotherapy and pembrolizumab-pemetrexed-platinum treatments showed survival reductions of 4.5 and 3.9 months, respectively (3.6 and 2.8 months corrected for QoL), with cost savings of €24,345 and €28,456. Sensitivity analyses confirmed consistent cost savings and survival reductions. Survival losses were mainly observed due to the lower survival rates associated with the alternative first-line treatment options available for non-responders in the predictive-biomarker-based strategy within each pembrolizumab-containing treatment regimen. Pembrolizumab-carboplatin-paclitaxel treatment also showed survival gains under certain conditions related to QoL and survival estimates.

Conclusions: Our study highlights the importance of careful de-implementation of ICI-treatments in advanced NSCLC, balancing costs reductions and side effects without comprising survival. In the pembrolizumab-carboplatin-paclitaxel treatment regimen, the survival loss could be considered negligible. Future research should define acceptable tradeoffs and thresholds for de-implementation, considering factors such as survival of alternative treatments and responder classification to guide predictive biomarker implementation and optimize health resource allocation.

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来源期刊
CiteScore
3.50
自引率
0.00%
发文量
64
审稿时长
8 weeks
期刊介绍: PharmacoEconomics - Open focuses on applied research on the economic implications and health outcomes associated with drugs, devices and other healthcare interventions. The journal includes, but is not limited to, the following research areas:Economic analysis of healthcare interventionsHealth outcomes researchCost-of-illness studiesQuality-of-life studiesAdditional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in PharmacoEconomics -Open may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.All manuscripts are subject to peer review by international experts. Letters to the Editor are welcomed and will be considered for publication.
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