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索托拉西布作为瑞士KRAS-G12C突变转移性非小细胞肺癌(mNSCLC)患者二线治疗的成本效益分析。

A cost-effectiveness analysis of sotorasib as second-line treatment for patients with KRAS-G12C-mutated metastatic non-small cell lung cancer (mNSCLC) in Switzerland.

作者信息

El Saadany Tämer, Lupatsch Judith, Mark Michael, Barbier Michaela, Mehra Tarun, Schwenkglenks Matthias, Von Moos Roger

机构信息

Division of Oncology/Hematology, Cantonal Hospital Graubünden, Chur, Switzerland.

Health Economics Facility, Department of Public Health, University of Basel, Basel, Switzerland.

出版信息

Swiss Med Wkly. 2025 Jan 6;155:3777. doi: 10.57187/s.3777.

Abstract

BACKGROUND AND OBJECTIVE

Because of the lack of effective targeted treatment options, docetaxel has long been the standard second-line therapy for patients with advanced non-small cell lung cancer, including the Kirsten rat sarcoma virus (KRAS) G12C mutation. The CodeBreak 200 trial demonstrated that sotorasib, a new drug targeting the G12C-mutated KRAS protein, modestly improved progression-free survival compared with docetaxel in patients whose cancer had progressed after receiving platinum chemotherapy and programmed cell death protein 1 (PD-1) / programmed death ligand 1 (PD-L1) inhibitors as first-line treatment. Consequently, sotorasib received temporary approval in Switzerland. Our analysis assessed the cost-effectiveness of sotorasib as a second-line treatment in Swiss patients with non-small cell lung cancer from the perspective of the Swiss statutory health insurance system.

METHODS

A partitioned survival model based on the CodeBreak 200 trial was constructed with a time horizon of 10 years and a discount rate of 3% for costs and quality-adjusted life years (QALYs). Parametric survival curves were fitted to the published Kaplan-Meier data, and survival was extrapolated. QALYs were obtained from the CodeBreak 100 trial and the literature. The costs of drugs, drug administration, diagnostics, disease management, and adverse events were considered. Because the price of sotorasib has not been established in Switzerland, two scenarios were analysed: the first used the published expected monthly United Kingdom (UK) price in Swiss francs (CHF 7870); the second used one-quarter of that price (CHF 1968), according to the lower dose used in the most recent trial, under the condition that one-quarter of the original sotorasib dose is equally effective. Treatment costs of adverse events were included.

RESULTS

Log-normal functions best fitted the survival curves from CodeBreak 200. For sotorasib versus docetaxel, our estimation showed no difference in QALYs (1.28 QALYs for both treatments), as the reduced adverse events reported in CodeBreak 200 for sotorasib had a minimal impact on the QALYs in our calculation. This made an incremental cost-effectiveness ratio (ICER) calculation irrelevant. Total per-patient costs were CHF 138,894 for the full sotorasib dose, CHF 82,741 for the one-quarter dose, and CHF 80,383 for docetaxel. These results were robust in 99% of probabilistic simulations.

CONCLUSION

Sotorasib did not demonstrate cost-effectiveness at the full dosage nor when reduced to a quarter of the dose. The primary factors motivating clinicians to prescribe sotorasib are its superior overall response rate compared with docetaxel and the reported improvement in patients' quality of life. These factors suggest that it would be reasonable to price it at approximately one-quarter of the assumed cost in the UK.

摘要

背景与目的

由于缺乏有效的靶向治疗方案,多西他赛长期以来一直是晚期非小细胞肺癌患者(包括携带 Kirsten 大鼠肉瘤病毒(KRAS)G12C 突变的患者)的标准二线治疗药物。CodeBreak 200 试验表明,索托拉西布是一种靶向 G12C 突变 KRAS 蛋白的新药,与多西他赛相比,在接受铂类化疗和程序性细胞死亡蛋白 1(PD-1)/程序性死亡配体 1(PD-L1)抑制剂作为一线治疗后癌症进展的患者中,可适度改善无进展生存期。因此,索托拉西布在瑞士获得了临时批准。我们的分析从瑞士法定医疗保险系统的角度评估了索托拉西布作为瑞士非小细胞肺癌患者二线治疗的成本效益。

方法

基于 CodeBreak 200 试验构建了一个分区生存模型,时间跨度为 10 年,成本和质量调整生命年(QALYs)的贴现率为 3%。将参数生存曲线拟合到已发表的 Kaplan-Meier 数据,并对生存情况进行外推。QALYs 来自 CodeBreak 100 试验和文献。考虑了药物、药物给药、诊断、疾病管理和不良事件的成本。由于索托拉西布在瑞士的价格尚未确定,分析了两种情况:第一种情况使用已公布的英国预期月价格换算为瑞士法郎(7870 瑞士法郎);第二种情况根据最近试验中使用的较低剂量,假设原索托拉西布剂量的四分之一具有同等疗效,使用该价格的四分之一(1968 瑞士法郎)。纳入了不良事件的治疗成本。

结果

对数正态函数最适合 CodeBreak 200 的生存曲线。对于索托拉西布与多西他赛,我们的估计显示 QALYs 无差异(两种治疗均为 1.28 QALYs),因为 CodeBreak 200 中报告的索托拉西布不良事件减少在我们的计算中对 QALYs 的影响最小。这使得增量成本效益比(ICER)计算无关紧要。全剂量索托拉西布的每位患者总费用为 138,894 瑞士法郎,四分之一剂量为 82,741 瑞士法郎,多西他赛为 80,383 瑞士法郎。这些结果在 99%的概率模拟中是稳健的。

结论

索托拉西布在全剂量及降至四分之一剂量时均未显示出成本效益。促使临床医生开具索托拉西布的主要因素是其与多西他赛相比更高的总体缓解率以及报告的患者生活质量改善。这些因素表明,将其定价为英国假设成本的约四分之一是合理的。

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