Clinical efficacy of Yiqi Yangyin Jiedu Formula combined with tislelizumab in treatment of driver‑gene‑negative advanced NSCLC and its impact on peripheral immune indicators

CAI Yuqing; LIU Fangfang; JIANG Yi; LIU Lingshuang

doi:10.16305/j.1007-1334.2024.z20240628008

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Clinical efficacy of Yiqi Yangyin Jiedu Formula combined with tislelizumab in treatment of driver‑gene‑negative advanced NSCLC and its impact on peripheral immune indicators

更新时间：2024-12-23

- Clinical efficacy of Yiqi Yangyin Jiedu Formula combined with tislelizumab in treatment of driver‑gene‑negative advanced NSCLC and its impact on peripheral immune indicators
- Shanghai Journal of Traditional Chinese Medicine Vol. 58, Issue 12, Pages: 130-136(2024)
- 作者机构：
  
  上海中医药大学附属龙华医院（上海 200032）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2024.z20240628008
  CLC：
- Published：10 December 2024，
  
  Received：28 June 2024，
- 稿件说明：
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蔡雨晴,刘芳芳,姜怡,等.益气养阴解毒方联合替雷利珠单抗治疗晚期驱动基因阴性NSCLC临床疗效及对外周免疫指标水平的影响[J].上海中医药杂志,2024,58(12):130-136.

CAI Yuqing,LIU Fangfang,JIANG Yi,et al.Clinical efficacy of Yiqi Yangyin Jiedu Formula combined with tislelizumab in treatment of driver‑gene‑negative advanced NSCLC and its impact on peripheral immune indicators[J].Shanghai Journal of Traditional Chinese Medicine,2024,58(12):130-136.
蔡雨晴,刘芳芳,姜怡,等.益气养阴解毒方联合替雷利珠单抗治疗晚期驱动基因阴性NSCLC临床疗效及对外周免疫指标水平的影响[J].上海中医药杂志,2024,58(12):130-136. DOI： 10.16305/j.1007-1334.2024.z20240628008.

CAI Yuqing,LIU Fangfang,JIANG Yi,et al.Clinical efficacy of Yiqi Yangyin Jiedu Formula combined with tislelizumab in treatment of driver‑gene‑negative advanced NSCLC and its impact on peripheral immune indicators[J].Shanghai Journal of Traditional Chinese Medicine,2024,58(12):130-136. DOI： 10.16305/j.1007-1334.2024.z20240628008.

摘要

目的

观察益气养阴解毒方联合程序性死亡受体-1（PD-1）抑制剂治疗晚期驱动基因阴性非小细胞肺癌（NSCLC）的协同增效作用，探索发挥疗效的外周免疫调控靶点。

方法

将84例初次接受PD-1抑制剂治疗的气阴两虚型晚期驱动基因阴性NSCLC患者进行分层区组随机化分组（治疗组42例、对照组42例），治疗组采用益气养阴解毒方联合含替雷利珠单抗方案的中西医结合治疗，对照组采用含替雷利珠单抗的纯西医治疗。主要终点指标为疾病控制率（DCR），次要观察指标为客观缓解率（ORR）、无进展生存期（PFS）、中医临床症状积分、中医证候疗效，同时检测包括调节性T细胞（Treg）及12种可溶性免疫检查点蛋白分子在内的外周免疫指标［主要包括可溶性转化生长因子-β（sTGF-β）、可溶性细胞毒T淋巴细胞相关抗原-4（sCTLA-4）、可溶性程序性死亡受体配体-1（sPD-L1）、可溶性T淋巴细胞免疫球蛋白黏蛋白-3（sTIM-3）、可溶性半乳糖凝集素-9（sGal-9）］表达水平。

结果

①最终81例患者数据纳入统计分析，治疗组41例、对照组40例。②治疗组DCR高于对照组（

0.05），中医证候疗效优于对照组（

0.05），神疲乏力、自汗盗汗、五心烦热评分的改善情况优于对照组（

0.05）。③治疗组、对照组中位PFS分别为9.2个月、6.5个月，差异有统计学意义（

0.05）；接受中西医结合方案治疗人群发生疾病进展的风险较单纯西医方案治疗降低44.7%［

=0.553，95%

（0.317，0.964），

=0.037］。④治疗2个疗程后与治疗前组内比较，治疗组CD8

T细胞表达水平升高（

0.05），Treg、sTGF-β、sCTLA-4、sPD-L1、sTIM-3及sGal-9表达水平降低（

0.05），对照组指标未见显著变化；治疗2个疗程后组间比较，两组CD8

T细胞、Treg、sTGF-β、sCTLA-4、sPD-L1及sGal-9表达水平差异有统计学意义（

0.05）。

结论

益气养阴解毒方联合含替雷利珠单抗方案治疗能够提高晚期驱动基因阴性NSCLC患者的DCR、延长PFS，并可改善患者气阴两虚证候，其机制可能与下调外周血Treg细胞、sTGF-β、sCTLA4、sPD-L1及sGal-9表达水平，提高CD8

T细胞比例，进而改善患者外周免疫环境有关。

Abstract

Objective

To observe the synergistic effect of Yiqi Yangyin Jiedu Formula （YYJF） combined with a programmed death receptor-1 （PD-1） inhibitor in the treatment of driver-gene-negative advanced non-small cell lung cancer （NSCLC）， and to explore the peripheral immune regulation targets that contribute to its efficacy.

Methods

Eighty-four patients with driver-gene-negative advanced NSCLC of qi-yin dual deficiency syndrome， who were receiving PD-1 inhibitor treatment for the first time， were stratified and randomized into two groups （treatment group with 42 patients， and control group with 42 patients）. In the treatment group， a combination of traditional Chinese and Western medicine treatment was received， which included YYJF combined with the regimen containing tislelizumab， while the control group received only the Western medicine regimen containing tislelizumab. The primary endpoint was disease control rate （DCR）， and secondary endpoints included objective response rate （ORR）， progression-free survival （PFS）， traditional Chinese medicine （TCM） clinical symptom scores， and TCM syndrome efficacy. Peripheral immune indicators， including regulatory T cells （Treg） and 12 soluble immune checkpoint proteins ［notably soluble transforming growth factor-β （sTGF-β）， soluble cytotoxic T lymphocyte antigen-4 （sCTLA-4）， soluble programmed death ligand 1 （sPD-L1）， soluble T-cell immunoglobulin and mucin domain-containing molecule-3 （sTIM-3）， and soluble galectin-9 （sGal-9）］， were also measured.

Results

①Finally， data from 81 patients were analyzed statistically， with 41 cases in the treatment group and 40 cases in the control group. ②The DCR was higher in the treatment group than that in the control group （

0.05）， and the TCM syndrome efficacy was superior to that of the control group （

0.05）. Improvements in symptoms such as fatigue， spontaneous sweating， night sweating， and feverish sensation in the palms， soles， and chest were significantly better in the treatment group （

0.05）. ③The median PFS was 9.2 months in the treatment group and 6.5 months in the control group， showing a statistically significant difference （

0.05）. Compared to the Western medicine-only group， the TCM and Western medicine combined treatment lowered the risk of disease

progression by 44.7% ［

=0.553， 95%

（0.317， 0.964），

=0.037］. ④After two courses of treatment， CD8

T cell expression levels increased （

0.05）， and Treg， sTGF-β， sCTLA-4， sPD-L1， sTIM-3， and sGal-9 expression levels decreased （

0.05） within the treatment group， while no significant changes were observed in the control group. Intergroup comparisons after two courses showed significant differences in the expression levels of CD8

T cells， Treg， sTGF-β， sCTLA-4， sPD-L1， and sGal-9 between the two groups （

0.05）.

Conclusion

The combination of YYJF and tislelizumab-containing regimen can improve the DCR and prolong PFS in patients with driver-gene-negative advanced NSCLC. The combined treatment also ameliorates the qi-yin dual deficiency syndrome. The mechanism may be related to downregulating the expression levels of Treg cells， sTGF-β， sCTLA-4， sPD-L1， and sGal-9 in peripheral blood， increasing the proportion of CD8

T cells， thereby improving the peripheral immune environment in patients.

关键词

非小细胞肺癌程序性死亡受体-1抑制剂益气养阴解毒方免疫治疗中医药疗法临床试验

Keywords

non-small cell lung cancerPD-1 inhibitorYiqi Yangyin Jiedu Formulaimmunotherapytraditional Chinese medicine therapyclinical trial

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