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非小细胞肺癌患者的生物标志物特异性生存率和药物成本

Biomarker-Specific Survival and Medication Cost for Patients With Non-Small Cell Lung Cancer.

作者信息

Tan Juanyi, Yang Szu-Chun, Dinan Michaela A, Chiang Anne C, Gross Cary P, Wang Shi-Yi

机构信息

Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.

Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut.

出版信息

JAMA Netw Open. 2025 Jun 2;8(6):e2514519. doi: 10.1001/jamanetworkopen.2025.14519.

DOI:10.1001/jamanetworkopen.2025.14519
PMID:40493365
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12152704/
Abstract

IMPORTANCE

Targeted therapies and immunotherapies prolong survival but are associated with high costs for patients with advanced non-small cell lung cancer (aNSCLC). To date, little is known about survival and medication cost by biomarker status in the US.

OBJECTIVE

To estimate survival and medication cost by aNSCLC biomarker status.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study using Flatiron Health data identified patients diagnosed with aNSCLC from January 1, 2016, through December 31, 2022. Each patient had received at least 1 biomarker test and 1 documented line of therapy; follow-up was through September 31, 2023. Patients were categorized based on the presence of driver alterations, including ALK rearrangement, BRAF variation, or EGFR variation. Patients without driver alterations were divided into 3 groups based on their programmed cell death 1 ligand 1 (PD-L1) expression (<1%, 1%-49%, or ≥50%).

MAIN OUTCOMES AND MEASURES

The primary outcome was medication costs, which were a function of survival probability and monthly medication costs. The secondary outcome was medication costs per survivor, defined as the mean aggregate medication costs within each patient cohort for each 1- or 2-year survivor.

RESULTS

The study cohort consisted of 26 635 patients with aNSCLC (mean [SD] age at diagnosis, 68.9 [10.0] years; 13 750 [52%] male; 2610 [10%] African American, 687 [3%] Asian, 18 352 [69%] White, and 4986 [19%] other race, including any race other than African American, Asian, or White). The median overall survival was 39.9 (95% CI, 33.9-48.5) months for patients with ALK rearrangement, 27.0 (95% CI, 24.8-28.8) months for EGFR variation, 18.7 (95% CI, 16.0-20.6) months for BRAF variation, 12.3 (95% CI, 12.0-12.7) months for PD-L1 less than 1%, 13.7 (95% CI, 13.1-14.3) months for PD-L1 of 1% to 49%, and 16.2 (95% CI, 15.3-17.0) months for PD-L1 of 50% or greater. The 1- and 2-year medication costs per patient for the overall cohort were $120 420 (95% CI, $115 540-$126 470) and $182 560 (95% CI, $172 900-$196 040), respectively. Patients with EGFR variation or PD-L1 of 50% or greater incurred relatively higher 1-year medication cost ($131 700 [95% CI, $125 340-$138 280] and $123 590 [95% CI, $115 970-$130 840], respectively) compared with patients with PD-L1 less than 1% ($110 350 [95% CI, $101 680-$120 040]). Patients with ALK rearrangement or EGFR variation incurred the highest 2-year medication cost ($242 130 [95% CI, $206 220-$267 330] and $241 940 [95% CI, $230 840-$254 730], respectively), whereas patients with PD-L1 less than 1% and PD-L1 of 1% to 49% had the lowest 2-year medication cost ($156 340 [95% CI, $142 450-$172 800] and $163 410 [95% CI, $152 410-$174 180], respectively). The medication costs per 1-year survivor were $152 370 (95% CI, $133 550-$178 080) for patients with ALK rearrangement, $175 720 (95% CI, $167 330-$185 390) for EGFR variation, $211 100 (95% CI, $195 030-$229 400) for PD-L1 less than 1%, $210 260 (95% CI, $193 190-$226 580) for PD-L1 of 1% to 49%, and $211 630 (95% CI, $198 670-$224 210) for PD-L1 of 50% or greater, whereas the costs per 2-year survivor were $363 480 (95% CI, $314 710-$401 320) for patients with ALK rearrangement, $468 400 (95% CI, $441 340-$497 860) for patients with PD-L1 of 50% or greater, $460 790 (95% CI, $427 340-$494 080) for patients with PD-L1 of 1% to 49%, and $500 220 (95% CI, $456 900-$556 730) for patients with PD-L1 less than 1%.

CONCLUSIONS AND RELEVANCE

In this cohort study, patients with aNSCLC with driver alterations experienced better survival and incurred lower medication costs per survivor than those without driver variation, indicating the need to develop more affordable and effective medications for patients without driver alterations.

摘要

重要性

靶向治疗和免疫治疗可延长晚期非小细胞肺癌(aNSCLC)患者的生存期,但这些患者面临着高昂的费用。迄今为止,在美国,关于生物标志物状态与生存期及药物成本的关系鲜为人知。

目的

评估aNSCLC患者按生物标志物状态划分的生存期和药物成本。

设计、设置和参与者:这项回顾性队列研究使用Flatiron Health数据,确定了2016年1月1日至2022年12月31日期间被诊断为aNSCLC的患者。每位患者至少接受了1次生物标志物检测和1次有记录的治疗方案;随访至2023年9月31日。患者根据是否存在驱动基因突变进行分类,包括ALK重排、BRAF变异或EGFR变异。无驱动基因突变的患者根据程序性细胞死亡1配体1(PD-L1)表达水平(<1%、1%-49%或≥50%)分为3组。

主要结局和指标

主要结局是药物成本,它是生存概率和每月药物成本的函数。次要结局是每位存活患者的药物成本,定义为每个患者队列中每1年或2年存活者的平均总药物成本。

结果

研究队列包括26635例aNSCLC患者(诊断时的平均[标准差]年龄为68.9[10.0]岁;13750例[52%]为男性;2610例[10%]为非裔美国人,687例[3%]为亚洲人,18352例[69%]为白人,4986例[19%]为其他种族,包括除非裔美国人、亚洲人或白人以外的任何种族)。ALK重排患者的中位总生存期为39.9(95%CI,33.9-48.5)个月,EGFR变异患者为27.0(95%CI,24.8-28.8)个月,BRAF变异患者为18.7(95%CI,16.0-20.6)个月,PD-L1<1%的患者为12.3(95%CI,12.0-12.7)个月,PD-L1为1%-49% 的患者为13.7(95%CI,13.1-14.3)个月,PD-L1≥50%的患者为16.2(95%CI,15.3-17.0)个月。整个队列中每位患者1年和2年的药物成本分别为120420美元(95%CI,115540-126470美元)和182560美元(95%CI,172900-196040美元)。与PD-L1<1%的患者(110350美元[95%CI,101680-120040美元])相比,EGFR变异或PD-L1≥50%的患者1年药物成本相对较高(分别为131700美元[95%CI,125340-138280美元]和123590美元[95%CI,115970-130840美元])。ALK重排或EGFR变异的患者2年药物成本最高(分别为242130美元[95%CI,206220-267330美元]和241940美元[95%CI,230840-254730美元]),而PD-L1<1%和PD-L1为1%-49%的患者2年药物成本最低(分别为156340美元[95%CI,142450-172800美元]和163410美元[95%CI,152410-174180美元])。ALK重排患者每1年存活者的药物成本为152370美元(95%CI,133550-178080美元),EGFR变异患者为175720美元(95%CI,167330-185390美元),PD-L1<1%的患者为211100美元(95%CI,195030-229400美元),PD-L1为1%-49%的患者为210260美元(95%CI,193190-226580美元),PD-L1≥50%的患者为211630美元(95%CI,198670-224210美元),而每2年存活者的成本方面,ALK重排患者为363480美元(95%CI,314710-401,320美元),PD-L1≥50%的患者为468400美元(95%CI,441340-497860美元),PD-L1为1%-49%的患者为460790美元(95%CI,427340-494080美元),PD-L1<1%的患者为50022万美元(95%CI,456900-556730美元)。

结论与意义

在这项队列研究中,与无驱动基因突变的患者相比,有驱动基因突变的aNSCLC患者生存期更长,每位存活患者的药物成本更低,这表明需要为无驱动基因突变的患者开发更经济有效的药物。

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