Modelling the Effectiveness of Tepotinib in Comparison to Standard-of-Care Treatments in Patients with Advanced Non-small Cell Lung Cancer (NSCLC) Harbouring METex14 Skipping in the UK.

IF 4.4 3区 医学 Q2 ONCOLOGY Targeted Oncology Pub Date : 2024-03-01 Epub Date: 2024-03-16 DOI:10.1007/s11523-024-01038-z
Rachael Batteson, Emma Hook, Hollie Wheat, Anthony J Hatswell, Helene Vioix, Thomas McLean, Stamatia Theodora Alexopoulos, Shobhit Baijal, Paul K Paik
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Abstract

Background: Patients with non-small cell lung cancer harbouring mesenchymal-epithelial transition exon 14 (METex14) skipping typically demonstrate poorer prognosis than overall non-small cell lung cancer. Until recently, no targeted treatments were available for patients with non-small cell lung cancer harbouring METex14 skipping in the UK, with limited treatments available.

Objective: This study estimates the long-term survival and quality-adjusted life-year benefit of MET inhibitor tepotinib versus current standard of care from a UK perspective.

Methods: A partitioned-survival model assessed the survival and quality-adjusted life-year benefits of tepotinib versus immunotherapy ± chemotherapy and chemotherapy for untreated and previously treated patients, respectively, using evidence from the single-arm VISION trial (NCT02864992). Two approaches were used to inform an indirect treatment comparison: (1) published clinical trials in overall non-small cell lung cancer and (2) real-world evidence in the METex14 skipping population. Results are presented as median and total quality-adjusted life-year gain and survival for progression-free survival and overall survival. Survival curves were validated against the external literature and uncertainty assessed using a probabilistic sensitivity analysis.

Results: Using the indirect treatment comparison against the published literature, tepotinib is estimated to have a median progression-free survival gain versus pembrolizumab ± chemotherapy (11.0 and 9.2 months) in untreated patients, and docetaxel ± nintedanib (5.1 and 6.4 months) in previously treated patients. Across the populations, tepotinib is estimated to have a median survival gain of 15.4 and 9.2 months versus pembrolizumab ± chemotherapy in untreated patients and 12.8 and 5.1 months versus docetaxel ± nintedanib in previously treated patients. The total quality-adjusted life-year gain ranges between 0.56 and 1.17 across the untreated and previously treated populations. Results from the real-world evidence of indirect treatment comparisons are consistent with these findings.

Conclusions: Despite the limitations of the evidence base, the numerous analyses conducted have consistently indicated positive outcomes for tepotinib versus the current standard of care.

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在英国,对携带 METex14 跳变的晚期非小细胞肺癌 (NSCLC) 患者进行特泊替尼疗效与常规治疗的比较建模。
背景:携带间充质-上皮转化外显子 14 (METex14) 缺失的非小细胞肺癌患者的预后通常比整体非小细胞肺癌患者要差。直到最近,英国还没有针对携带 METex14 跳越的非小细胞肺癌患者的靶向治疗,可用的治疗方法也很有限:本研究从英国的角度估算了 MET 抑制剂特泊替尼与现行标准治疗相比的长期生存率和质量调整生命年收益:方法:利用单臂VISION试验(NCT02864992)的证据,采用分区生存期模型评估了特泊替尼与免疫疗法±化疗和化疗对未治疗和既往治疗患者的生存期和质量调整生命年的益处。间接治疗比较采用了两种方法:(1) 已发表的非小细胞肺癌总体临床试验;(2) METex14跳过人群的实际证据。结果显示为无进展生存期和总生存期的中位数和总质量调整生命年收益及生存率。根据外部文献对生存曲线进行了验证,并使用概率敏感性分析对不确定性进行了评估:通过与已发表文献进行间接治疗比较,估计在未经治疗的患者中,特泊替尼与pembrolizumab±化疗(11.0个月和9.2个月)相比,无进展生存期中位数增加;在既往接受过治疗的患者中,多西他赛±宁替达尼(5.1个月和6.4个月)相比,无进展生存期中位数增加。据估计,在所有人群中,在未经治疗的患者中,特泊替尼与pembrolizumab±化疗相比,中位生存期分别延长了15.4个月和9.2个月;在既往接受过治疗的患者中,特泊替尼与多西他赛±尼替达尼相比,中位生存期分别延长了12.8个月和5.1个月。在未经治疗和既往接受过治疗的人群中,总质量调整生命年收益介于0.56和1.17之间。来自真实世界的间接治疗比较证据的结果与这些发现一致:尽管证据基础存在局限性,但所进行的大量分析一致表明,与目前的标准治疗相比,特泊替尼具有积极的疗效。
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来源期刊
Targeted Oncology
Targeted Oncology 医学-肿瘤学
CiteScore
8.40
自引率
3.70%
发文量
64
审稿时长
>12 weeks
期刊介绍: Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.
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