葛根芩连片减轻非小细胞肺癌患者免疫相关不良事件：中国一项多中心随机对照试验

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-15 DOI:10.1016/j.phymed.2025.156968

Xingyu Lu , Aolin Wang , Dongna Chen , Meng Yang , Yongming Zhang , Meng Liu , Xiaoyan Zhang , Yuan Li , Daiwei Liu , Yunliang Wang , Zhiqiang Cheng , Liya Li , Huijuan Cui

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引用次数: 0

摘要

免疫相关不良事件（irAEs）严重影响患者的生活质量，限制了免疫治疗的应用。葛根芩连片（GQT）是一种经典的中草药配方，已显示出缓解irAEs的潜力。然而，支持GQT作为免疫检查点抑制剂（ICI）治疗晚期非小细胞肺癌（NSCLC）的协同疗法的临床证据仍然不足。目的评价GQT降低非小细胞肺癌ICI治疗中irae发生率的有效性和安全性。研究设计：一项多中心、开放标签、随机对照试验。方法将符合条件的患者按1:1比例随机分为ICI +化疗+ GQT组（GQT组）或ICI +化疗组（对照组）。主要观察指标是irAEs的发生率和严重程度。次要结局包括客观缓解率（ORR）和疾病控制率（DCR）。在基线和治疗后评估血清白细胞介素-6 （IL-6）和肿瘤坏死因子α (TNF-α)水平。结果从2022年10月至2024年8月，94名参与者在中国四家医院随机分为GQT组（n = 47）和对照组（n = 47）。GQT组irae发生率明显低于对照组[31.91%（15/47）比59.57% (28/47),p = 0.007, 95% CI: 0.137 ~ 0.741]。GQT组没有患者出现多系统毒性，而对照组有3例（3/ 28,10.7%）。GQT组irae的中位发病时间为14.9周，对照组为8.7周（p = 0.807）。在反应可评估的患者中，GQT组（n = 45）的ORR为48.9% (0 CR, 23 PR)，对照组（n = 43）的ORR为36.2% (1 CR, 16 PR) （p = 0.211, 95% CI: 0.686-3.725）。GQT组治疗3个周期后IL-6水平显著降低(p <；0.001)，可能有助于降低irae的发生率。结论在接受ICI治疗的晚期NSCLC患者中，qt可显著降低irae的发生率，延长irae的中位发病时间。观察到的效果可能与IL-6的下调有关。GQT有望作为一种协同治疗，减轻irae，并可能提高ICIs的治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Gegen Qinlian Tablets attenuate immune-related adverse events in NSCLC patients: A multi-center randomized controlled trial in China

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Gegen Qinlian Tablets attenuate immune-related adverse events in NSCLC patients: A multi-center randomized controlled trial in China

Background

Immune related adverse events (irAEs) significantly compromise patients’ quality of life and limit the application of immunotherapy. Gegen Qinlian Tablets (GQT), a classical Chinese herbal formula, have shown potential in mitigating irAEs. However, clinical evidence supporting the use of GQT as a synergy therapy for immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC) remains insufficient.

Purpose

To evaluate the efficacy and safety of GQT in reducing the incidence of irAEs in NSCLC with ICI treatment.

Study design

A multi-center, open-label, randomized controlled trial.

Methods

Eligible patients were randomly assigned (1:1) to receive ICI plus chemotherapy plus GQT (GQT group) or ICI plus chemotherapy alone (control group). The primary outcome was the incidence and severity of irAEs. Secondary outcomes included objective response rate (ORR) and disease control rate (DCR). Serum levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were assessed at baseline and after treatment.

Results

From October 2022 to August 2024, 94 participants were randomized to the GQT group (n = 47) or the control group (n = 47) at four hospitals in China. The incidence of irAEs was significantly lower in the GQT group than in the control group [31.91 % (15/47) vs. 59.57 % (28/47), p = 0.007, 95 % CI: 0.137–0.741]. No patient in the GQT group experienced multi-systemic toxicity, whereas 3 patients in the control group did (3/28, 10.7 %). The median onset time of irAEs in the GQT group was 14.9 weeks, and was 8.7 weeks in the control group (p = 0.807). Among response-evaluable patients, the ORR was 48.9 % (0 CR, 23 PR) in the GQT group (n = 45), and 36.2 % (1 CR, 16 PR) in the control group (n = 43) (p = 0.211, 95 % CI: 0.686–3.725). IL-6 level significantly decreased after 3 treatment cycles in the GQT group (p < 0.001), potentially contributing to the reduced incidence of irAEs.

Conclusion

GQT significantly reduced the incidence of irAEs and prolonged the median onset time of irAEs in patients with advanced NSCLC receiving ICI therapy. The observed effects may be associated with the downregulation of IL-6. GQT showed promise as a synergistic treatment that mitigated irAEs and might enhance the therapeutic efficacy of ICIs.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.