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PD-L1 对非小细胞肺癌患者生存和免疫检查点抑制剂价值的影响;建议、政策和展望。

The impact of PD-L1 on survival and value of the immune check point inhibitors in non-small-cell lung cancer; proposal, policies and perspective.

机构信息

Hematology-Oncology Section, Department of Medicine, University of California, Irvine, California, USA.

出版信息

J Immunother Cancer. 2018 Feb 20;6(1):15. doi: 10.1186/s40425-018-0320-3.

Abstract

BACKGROUND

The impact of programmed death receptor-ligand1 (PD-L1) on costs and value of the immune check point inhibitors (ICPI) has received minimal attention.

OBJECTIVES

1- Design a sliding scale to grade survival in 2nd-line non-small-cell lung cancer (NSCLC). 2- Compare costs and value of Nivolumab (Nivo), Atezolizumab (Atezo) and Pembrolizumab (Pembro) vs. Docetaxel (Doc).

METHODS

Previously reported median overall survival (OS) and prices posted by parent company were utilized. The OS gains over controls in days were graded (gr) from A+ to D. Docetaxel costs were calculated for 6-12 cycles and the ICPI for 1 year. Adverse events treatment costs (AEsTC) were reported separately. The cost/life-year gain (C/LYG) was computed as drug yearly-cost/OS gain over control in days × 360 days. The relative value of the ICPI were expressed as $100,000/C/LYG.

RESULTS

Costs of Doc 6 cycles were $23,868, OS/gr 87/C, AEs gr ¾ > 20%, AEsTC $1978 and 6- 12 cycle C/LYG $98,764 -$197,528. Nivo, Atezo and Pembro gr ¾ were < 20% at average costs of $1480. In non-squamous NSCLC, Nivo demonstrated OS/g 84/C and C/LYG $558,326 as compared with 264/A and $177,645 in PD-L1 > 10%. Atezolizumab OS/g were 87/B and C/LYG $551,407 improving in enriched PD-L1 to 162/A and $332,020 respectively. Pembrolizumab in PD-L1 > 1.0% demonstrated OS/g 57/C and C/LYG $659,059 improving in > 50% PD-L1 to 201/A and $186,897. PD-L1 enrichment increased RV of Nivo from 0.18 to 0.56, Atezo from 0.16 to 0.66 and Pembro from 0.15 to 0.53.

CONCLUSIONS

Simplified methodology to grade OS and weigh value of anticancer drugs was proposed. In 2nd-line non-squamous NSCLC, value of Doc, Nivo, Atezo and Pembro regardless of PDL-1 expression were limited and modest. Enrichment of PD-L1 resulted in unprecedented OS, improved grades and enhanced value at seemingly justifiable costs.

摘要

背景

程序性死亡受体配体 1(PD-L1)对免疫检查点抑制剂(ICPI)的成本和价值的影响受到的关注很少。

目的

  1. 设计一个用于二线非小细胞肺癌(NSCLC)的生存分级的滑动量表。2. 比较纳武单抗(Nivo)、阿特珠单抗(Atezo)和派姆单抗(Pembro)与多西他赛(Doc)的成本和价值。

方法

利用先前报道的中位总生存期(OS)和母公司公布的价格。将 OS 相对于对照组的每日获益从 A+到 D 进行分级。计算多西他赛 6-12 个周期和 ICPI 1 年的成本。分别报告不良反应治疗成本(AEsTC)。计算生命年获益成本比(C/LYG),方法为药物每年成本/与对照组相比的 OS 获益天数×360 天。将 ICPI 的相对价值表示为每 10 万美元/C/LYG。

结果

多西他赛 6 个周期的成本为 23868 美元,OS/gr87/C,AEsgr3/4>20%,AEsTC1978 美元,6-12 个周期的 C/LYG98764-197528 美元。Nivo、Atezo 和 Pembro 的 gr3/4<20%,平均成本为 1480 美元。在非鳞状 NSCLC 中,Nivo 显示 OS/g84/C 和 C/LYG558326 美元,与 PD-L1>10%时的 264/A 和 177645 美元相比。阿特珠单抗 OS/g87/B 和 C/LYG551407 美元在富集 PD-L1 时分别提高到 162/A 和 332020 美元。在 PD-L1>1.0%时,派姆单抗的 OS/g57/C 和 C/LYG659059 美元,在 PD-L1>50%时分别提高到 201/A 和 186897 美元。PD-L1 富集使 Nivo 的 RV 从 0.18 增加到 0.56,Atezo 从 0.16 增加到 0.66,Pembro 从 0.15 增加到 0.53。

结论

提出了一种用于评估癌症药物 OS 和权衡价值的简化方法。在二线非鳞状 NSCLC 中,无论 PD-L1 表达如何,多西他赛、Nivo、Atezo 和 Pembro 的药物价值都很有限,而且适中。PD-L1 富集带来了前所未有的 OS 获益、改善的分级和在看似合理的成本下提高的价值。

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