清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Determinants of Response to Sequential Pembrolizumab with Trastuzumab Plus Platinum/5FU in HER2-positive Gastric Cancer: A Phase II Chemoimmunotherapy Trial

化学免疫疗法 曲妥珠单抗 彭布罗利珠单抗 医学 肿瘤科 内科学 癌症 临床研究阶段 化疗 免疫疗法 乳腺癌
作者
Sung Hee Lim,Minae An,Hyuk Lee,You Jeong Heo,Byung‐Hoon Min,Arnav Mehta,Samuel J. Wright,Kyoung‐Mee Kim,Seung Tae Kim,Samuel J. Klempner,Jeeyun Lee
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
标识
DOI:10.1158/1078-0432.ccr-24-3528
摘要

Abstract Purpose: Adding pembrolizumab to first-line 5FU/platinum chemotherapy plus trastuzumab improves outcomes in advanced HER2+ gastroesophageal adenocarcinomas, but the benefit is largely confined to dual HER2+ and PD-L1+ patients. To assess the contributions of components, we conducted a phase II trial evaluating 5FU/platinum/trastuzumab and added pembrolizumab in cycle 2 in patients with metastatic HER2+ disease. Patients and Methods: Treatment naive advanced HER2+ gastroesophageal cancer patients underwent a baseline biopsy, and received a single dose of 5FU/platinum with trastuzumab followed by repeat biopsy. Pembrolizumab was added, and a third biopsy was performed after 6 cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression free (PFS), and overall survival. Exploratory biomarker analysis and dynamic changes in HER2 and PD-L1 were prespecified. Results: Sixteen patients were enrolled. The ORR was 69%, and the median PFS was 11.9 months. Serial whole-exome, single-cell RNA, T-cell receptor sequencing and spatial transcriptomics from pre-treatment and on-treatment samples revealed early trastuzumab-induced natural killer cell infiltration in HER2+ tumor beds and an increase in Fc receptor (FcR) gamma III expression in macrophages, suggesting that trastuzumab directs FcR-mediated antibody-dependent cytotoxicity. This favorable remodeling was enhanced by the addition of pembrolizumab, primarily in PD-L1+ samples. We observed TGF-β signaling in HER2-negative tumor regions, which was associated with non-responder status. Conclusions: These data highlight the biology of intratumoral heterogeneity, and the impact of tumor and immune cell features on clinical outcomes and may partly explain the lesser magnitude of pembrolizumab benefit in HER2+ and PD-L1 negative subgroups.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
17秒前
香蕉觅云应助科研通管家采纳,获得10
22秒前
Owen应助科研通管家采纳,获得10
22秒前
海藏进星辰完成签到,获得积分10
36秒前
卷卷完成签到,获得积分10
40秒前
43秒前
ktw完成签到,获得积分10
44秒前
kmzzy完成签到,获得积分10
1分钟前
科研通AI2S应助科研通管家采纳,获得10
2分钟前
3分钟前
3分钟前
一条摆摆的沙丁鱼完成签到 ,获得积分10
4分钟前
4分钟前
yyf发布了新的文献求助10
4分钟前
claud完成签到 ,获得积分0
4分钟前
yyf完成签到,获得积分10
4分钟前
ffdhdh完成签到,获得积分10
4分钟前
白天科室黑奴and晚上实验室牛马完成签到 ,获得积分10
6分钟前
6分钟前
Akim应助亦风采纳,获得10
6分钟前
6分钟前
亦风发布了新的文献求助10
6分钟前
情怀应助刘紫媛采纳,获得10
6分钟前
科研通AI2S应助亦风采纳,获得10
6分钟前
亦风完成签到,获得积分10
6分钟前
7分钟前
偷得浮生半日闲完成签到 ,获得积分10
7分钟前
jintian完成签到 ,获得积分10
7分钟前
7分钟前
fufufu123完成签到 ,获得积分10
8分钟前
桐桐应助科研通管家采纳,获得10
8分钟前
puzhongjiMiQ完成签到,获得积分10
8分钟前
9分钟前
李健的粉丝团团长应助lzzz采纳,获得10
9分钟前
9分钟前
刘紫媛发布了新的文献求助10
10分钟前
Raul完成签到 ,获得积分10
10分钟前
lql完成签到 ,获得积分10
10分钟前
可爱的函函应助鲅鱼圈采纳,获得10
11分钟前
11分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3990469
求助须知:如何正确求助?哪些是违规求助? 3532166
关于积分的说明 11256513
捐赠科研通 3271046
什么是DOI,文献DOI怎么找? 1805207
邀请新用户注册赠送积分活动 882302
科研通“疑难数据库(出版商)”最低求助积分说明 809234