• 患者服务: 与癌共舞小助手
  • 微信号: yagw_help22

QQ登录

只需一步,快速开始

开启左侧

[基础知识] 给ICB免疫减毒增效的 药物(十九)--肌苷、β-葡聚糖

[复制链接]
5037 0 自学自救 发表于 2025-4-3 17:11:20 |

马上注册,结交更多好友,享用更多功能,让你轻松玩转社区。

您需要 登录 才可以下载或查看,没有账号?立即注册

x
第一部分 肌苷, B$ O$ j# K) z
" E  B  n# P: ^+ |" x' U' H

& v. [5 @0 R8 U9 h! p' T《Inosine enhances the efficacy of immune-checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study》 一文介绍了一项前瞻性随机对照二期临床试验:* D; y) L% W! m  T" d# E; Y) V7 }$ V
4 C0 r( d$ v: {- Z
1、入组患者:172名晚期实体瘤患者,分为 ICB免疫治疗+肌苷组和 ICB免疫治疗组不联合肌苷(该组部分患者联合了化疗或者靶向)两组,每组86名患者。
5 B2 J, H) T# a; t: `   d# F/ y+ }- H! p
2、肌苷用法:口服肌苷片,每天三次,每次0.2克。
& K- E4 N! S8 |% q& ` 6 c$ p2 G7 _" j
3、试验结果:肌苷组和非肌苷组中位PFS (95% CI)分别为7.00(5.31-8.69)和4.40(3.10-5.70)个月(风险比[HR]0.63;95%置信区间为0.44–0.90,p= 0.011),肌苷组PFS提高有统计学意义。ORR分别为26.7%和15.1%(p= 0.061),肌苷组ORR有改善。非肌苷组中位OS为29.67个月(95% CI 17.40–41.94),肌苷组中位OS尚未达到。
8 }7 o3 l) K, g0 H" Z 9 _$ ~3 R7 u* Q* {8 M& q, X$ O
肌苷组和非肌苷组分别有25名(29%)和31名(36%)患者出现3级和4级不良反应,肌苷组的不良反应趋于减少。$ a9 S2 A$ o. C; q* F6 S! u( R

( U: T* k5 ~4 ^* ^2 x% j& |
6 A! I5 n+ a+ ~( ^! b& E
9 ]2 k, v" I% ~0 _0 `: Z' B& V( g第二部分 β-葡聚糖  W$ t7 G6 K  W! j
* g% X1 D- ?- U$ w* P4 j4 W
' ~  X4 t/ [" Z- q
《β-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer》一文介绍了一项前瞻性随机对照二期临床试验,β-葡聚糖+pd-1i 恩沃利 + 抗血管生成药物治疗先前pd-1i治疗失败的非小细胞肺癌。
5 ?# Z9 {1 P3 C* X& A1 Q/ {& Z# a
7 Q: H; c1 A- d  O+ [: O. @1、入组患者:23名晚期非小细胞肺癌患者,这些患者之前用pd-1i治疗都已经失败。
2 p4 z( T$ i/ ?; v 0 t  D: H* k! s7 {; m
2、β-葡聚糖用法:每天两次,每次500毫克。
) [% o( C' I7 d3 q
8 y; d; ~+ t# V  W* ^3、试验结果:ORR 21.7%,DCR 73.9%.,PFS 4.3个月,OS 8.9个月。PD-L1阳性和阴性亚组之间的mPFS有显著差异(6.3个月对2.3个月,p = 0.002)。9 ^: f7 S- F  i) i  s$ h

  Y( b  j! b* \1 ^. }1 T( }52.2%的患者发生了治疗相关的不良事件。最常见的原因是甲状腺功能减退(26.1%)和疲劳(26.1%)。报告了2例(8.7%)3级不良事件。未观察到与死亡相关的不良反应。4 ?' C) X' X, }* V# L' k
% q3 h, V! [% E  C) g4 [; F
蛋白质组学分析显示CASP-8、ARG1、MMP12、CD28和CXCL5的水平与对治疗的抗性相关,而CD40-L和EGF的水平与有利的反应相关。
$ f) y, e6 ^  F4 I2 @ 1 }7 z0 H3 Q8 a8 g, p" j3 J+ N$ s' q
(因为患者都是之前用pd-1i都已经失败的患者,所以ORR 21.7%,DCR 73.9% 还是很不错的)( ^' {* k5 n* w! Z, }
& R1 J9 N: j* l5 Y
3 m! d' s' B1 F2 O" q
I 《Inosine enhances the efficacy of immune-checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study》
, F! L9 B+ o! k4 S; c - _& H2 W+ X7 g  J& ^4 f4 j
Background: This study aimed to evaluate whether inosine enhances the efficacy of immune-checkpoint inhibitors in human malignant solid tumors.5 y2 {2 }$ ?3 |

& `' j! y7 v& q2 g, o% |Methods: This single-center, prospective, randomized, open-label study was conducted, from January 2021 to December 2022, in Beijing Friendship Hospital, Capital Medical University, and participants were randomly assigned (1:1) to either the inosine (trial) or non-inosine (control) group that received inosine (dosage: 0.2 g, three times/day) + PD-1/PD-L1 inhibitor or only PD-1/PD-L1 inhibitor ± targeted ± chemotherapy, respectively. Efficacy was assessed every 6 weeks (i.e., after every two-three treatment cycles). The primary endpoint was the objective response rate (ORR); the secondary endpoints were disease control rate, overall survival (OS), and progression-free survival (PFS). The trial was registered at ClinicalTrials.gov (NCT05809336).$ h4 m. n4 d. V8 [" t7 V4 o

, H9 L  ^+ s$ {- z, }! OResults: Among the 172 participants with advanced malignant solid tumors, 86 each were assigned to the inosine and non-inosine groups, wherein the median PFS (95% CI) was 7.00 (5.31-8.69) and 4.40 (3.10-5.70) months, respectively (hazard ratio [HR] 0.63; 95% CI 0.44-0.90, p = 0.011), and the ORR was 26.7% and 15.1%, respectively (p = 0.061). In the inosine and non-inosine groups, the median OS was not reached and was 29.67 (95% CI 17.40-41.94) months, respectively (HR 1.05 [95% CI 0.59-1.84], p = 0.874). Compared with the non-inosine group, the median PFS and ORR of the inosine group were significantly prolonged and improved in the multiple exploratory subgroup analyses. The safety analysis showed that Grades 3 and 4 adverse reactions occurred in 25 (29%) and 31 (36%) patients in the inosine and non-inosine groups, respectively, and tended to decrease in the inosine group compared with the non-inosine group.6 l7 O$ T0 W: Y- r, B, _
1 m( J0 P* g* f* P* U# p5 v1 `
Conclusion: Inosine had a tendency to enhance the efficacy of immune-checkpoint inhibitors and reduced immunotherapy-related adverse reactions.+ n- D4 f! w5 @0 ~% N' ~' m
. L9 k& n3 y0 D; l" A& q

3 S& N/ k- G: {. p$ w* k+ v* _; ?
% c! E  y0 a+ I9 z4 I* y# `II 《β-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer》
: S: w8 X( G1 O* [- F; @   Y) k) Q3 c, t7 A
Background: Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). β-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received β-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis.  C! `2 v3 S9 }9 a, \7 U8 O! R

( ?; s5 l  C4 aResults: Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0-6.6] and 9.8 months [95% CI: 7.2-12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response.( g1 `* J$ u" A
, F3 u6 `; \; k9 v; _3 k% O
Conclusion: β-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients.

发表回复

您需要登录后才可以回帖 登录 | 立即注册

本版积分规则

  • 回复
  • 转播
  • 评分
  • 分享
帮助中心
网友中心
购买须知
支付方式
服务支持
资源下载
售后服务
定制流程
关于我们
关于我们
友情链接
联系我们
关注我们
官方微博
官方空间
微信公号
快速回复 返回顶部 返回列表