雷莫西尤单抗在进展期胃癌/胃食管交界部癌患者中的疗效与安全性评估:一项回顾性观察性研究

doi:10.11904/j.issn.1002-3070.2025.06.010

实用肿瘤学杂志 ›› 2025, Vol. 39 ›› Issue (6): 527-534.doi: 10.11904/j.issn.1002-3070.2025.06.010

雷莫西尤单抗在进展期胃癌/胃食管交界部癌患者中的疗效与安全性评估:一项回顾性观察性研究

赵健¹, 柳长清², 盖一², 任静², 王育生³, 王广雨²

1.山西医科大学附属肿瘤医院消化科(太原 030013);
2.哈尔滨医科大学附属肿瘤医院胃肠肿瘤科;
3.山西医科大学第一医院肿瘤消化科

收稿日期:2024-12-26 修回日期:2025-03-08 出版日期:2025-12-28 发布日期:2026-01-13
通讯作者: 王广雨,E-mail:guangyuwang@hrbmu.edu.cn
作者简介:赵健,男,(1993—),硕士,主治医师,从事消化系统肿瘤的基础与临床研究。
基金资助:
1.国家自然科学基金面上项目(编号:82072740);2.白求恩·晚期消化肿瘤治疗临床研究计划项目(编号:J202301E034)

Evaluation of the efficacy and safety of ramucirumab in patients with advanced gastric cancer or gastroesophageal junction cancer:A retrospective observational study

ZHAO Jian¹, LIU Changqing², GAI Yi², REN Jing², WANG Yusheng³, WANG Guangyu²

1. Department of Digestive,Cancer Hospital Affiliated to Shanxi Medical University,Taiyuan 030013,China;
2. Department of Gastrointestinal Medical Oncology,Harbin Medical University Cancer Hospital;
3. Department of Oncology Digestive,the First Hospital of Shanxi Medical University

Received:2024-12-26 Revised:2025-03-08 Online:2025-12-28 Published:2026-01-13

摘要/Abstract

摘要： 目的利用真实世界数据,探索雷莫西尤单抗在中国进展期胃癌/胃食管交界部癌(gastric cancer/gastroesophageal junction cancer,GC/GEJC)患者中的疗效和安全性,并分析不同临床特征及联合治疗方案对患者生存的影响。方法本研究为双中心回顾性真实世界研究,纳入自2017年7月至2024年1月在山西医科大学附属肿瘤医院和哈尔滨医科大学附属肿瘤医院接受雷莫西尤单抗治疗的72例进展期GC/GEJC患者。以总生存期(overall survival,OS)为主要终点、无进展生存期(progression free survival,PFS)等为次要终点;采用生存分析方法评估并比较OS与PFS,并通过Cox比例风险模型分析患者OS和PFS的影响因素。结果所有患者中位PFS为4.27个月(95% CI:3.38~5.15个月),中位OS为9.66个月(95% CI:7.09~12.23个月)。在可评估疗效的49例患者中,客观缓解率(objective response rate,ORR)为16.3%,疾病控制率(disease control rate,DCR)为67.4%。多因素Cox回归分析显示,雷莫西尤单抗联合免疫检查点抑制剂(immune checkpoint inhibitor,ICI)治疗是OS的独立危险因素(HR=4.600,95% CI:1.700~12.452,P=0.003),而男性(HR=0.282,95% CI:0.116~0.685,P=0.005)与既往手术史(HR=0.401,95% CI:0.184~0.876,P=0.022)是OS的独立保护因素。安全性方面,75.0%(54/72)的患者发生不良事件,最常见的3~4级不良事件为中性粒细胞减少(8.3%),未发现新的安全性信号。结论本真实世界研究证实雷莫西尤单抗在进展期GC/GEJC患者中具有与关键临床试验一致的疗效和可控的安全性。然而,雷莫西尤单抗联合ICI治疗可能与生存期缩短相关,临床应用中应谨慎评估适用人群与潜在混杂因素,并有待前瞻性研究进一步验证。

关键词: 进展期胃癌, 进展期胃食管交界部癌, 雷莫西尤单抗, 真实世界研究

Abstract: Objective This study aimed to explore the efficacy and safety of ramucirumab in Chinese patients with advanced gastric cancer / gastroesophageal junction cancer(GC/GEJC)using real world data,and analyze the impact of different clinical characteristics and combination treatment regimens on patient survival. Methods This was a dual-center,retrospective real world study involving 72 patients with advanced GC/GEJC who received ramucirumab treatment at Shanxi Medical University Cancer Hospital and Harbin Medical University Cancer Hospital from July 2017 to January 2024.Overall survival(OS)was the primary endpoint,while progression free survival(PFS)and other outcomes served as secondary endpoints.Survival analysis methods were employed to evaluate and compare OS and PFS,and Cox proportional hazards model was used to analyze influencing factors of OS and PFS. Results The median PFS was 4.27 months(95% CI:3.38-5.15 months),and the median OS was 9.66 months(95% CI:7.09-12.23 months)for all patients.Among 49 evaluable patients,the objective response rate(ORR)was 16.3%,and the disease control rate(DCR)was 67.4%.Multivariate Cox regression analysis showed that ramucirumab combined with immune checkpoint inhibitor(ICI)was an independent risk factor for OS(HR=4.600,95% CI:1.700-12.452,P=0.003),while male(HR=0.282,95% CI:0.116-0.685,P=0.005)and a history of prior surgery(HR=0.401,95% CI:0.184-0.876,P=0.022)were independent protective factors for OS.In terms of safety,75.0%(54/72)of patients experienced adverse events,with neutropenia(8.3%)being the most common grade 3-4 adverse event.No new safety signals were identified. Conclusion This real world study confirms that ramucirumab demonstrates consistent efficacy and a manageable safety in patients with advanced GC/GEJC as observed in pivotal clinical trials.However,ramucirumab combined with ICIs may be associated with reduced survival,necessitating cautious assessment of patient suitability and potential confounders in clinical practice,with further prospective research required for validation.

Key words: advanced gastric cancer, advanced gastroesophageal junction cancer, ramucirumab, real world study

中图分类号:

R735.2

赵健, 柳长清, 盖一, 任静, 王育生, 王广雨. 雷莫西尤单抗在进展期胃癌/胃食管交界部癌患者中的疗效与安全性评估:一项回顾性观察性研究[J]. 实用肿瘤学杂志, 2025, 39(6): 527-534.

ZHAO Jian, LIU Changqing, GAI Yi, REN Jing, WANG Yusheng, WANG Guangyu. Evaluation of the efficacy and safety of ramucirumab in patients with advanced gastric cancer or gastroesophageal junction cancer:A retrospective observational study[J]. Journal of Practical Oncology, 2025, 39(6): 527-534.

参考文献

1 Bray F,Laversanne M,Sung H,et al.Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2024,74(3):229-263.
2 Fan X,Qin X,Zhang Y,et al.Screening for gastric cancer in China:advances,challenges and visions[J].Chin J Cancer Res,2021,33(2):168-180.
3 Joshi SS,Badgwell BD.Current treatment and recent progress in gastric cancer[J].CA Cancer J Clin,2021,71(3):264-279.
4 Kanagavel D,Fedyanin M,Tryakin A,et al.Second-line treatment of metastatic gastric cancer:current options and future directions[J]World J Gastroenterol,2015,21(41):11621-11635.
5 Bang YJ,Van Cutsem E,Feyereislova A,et al.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer(ToGA):a phase 3,open-label,randomised controlled trial[J].Lancet,2010,376(9749):687-697.
6 Peng Z,Liu T,Wei J,et al.Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing,locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase II study[J].Cancer Commun(Lond),2021,41(11):1173-1182.
7 Siena S,Di Bartolomeo M,Raghav K,et al.Trastuzumab deruxtecan(DS-8201)in patients with HER2-expressing metastatic colorectal cancer(DESTINY-CRC01):a multicentre,open-label,phase 2 trial[J].Lancet Oncol,2021,22(6):779-789.
8 Shitara K,Van Cutsem E,Bang YJ,et al.Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line,advanced gastric cancer:the KEYNOTE-062 phase 3 randomized clinical trial[J].JAMA Oncol,2020,6(10):1571-1580.
9 Janjigian YY,Shitara K,Moehler M,et al.First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric,gastro-oesophageal junction,and oesophageal adenocarcinoma(CheckMate 649):a randomised,open-label,phase 3 trial[J].Lancet,2021,398(10294):27-40.
10 Xu J,Jiang H,Pan Y,et al.Sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer:the ORIENT-16 randomized clinical trial[J].JAMA,2023,330(21):2064-2074.
11 Cotes Sanchís A,Gallego J,Hernandez R,et al.Second-line treatment in advanced gastric cancer:data from the Spanish AGAMENON registry[J].PLoS One,2020,15(7):e0235848.
12 Digklia A,Wagner AD.Advanced gastric cancer:current treatment landscape and future perspectives[J].World J Gastroenterol,2016,22(8):2403-2414.
13 Lieto E,Ferraraccio F,Orditura M,et al.Expression of vascular endothelial growth factor(VEGF)and epidermal growth factor receptor(EGFR)is an independent prognostic indicator of worse outcome in gastric cancer patients[J].Ann Surg Oncol,2008,15(1):69-79.
14 Murukesh N,Dive C,Jayson GC.Biomarkers of angiogenesis and their role in the development of VEGF inhibitors[J].Br J Cancer,2010,102(1):8-18.
15 Okines AF,Reynolds AR,Cunningham D.Targeting angiogenesis in esophagogastric adenocarcinoma[J].Oncologist,2011,16(6):844-858.
16 Fuchs CS,Tomasek J,Yong CJ,et al.Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(REGARD):an international,randomised,multicentre,placebo-controlled,phase 3 trial[J].Lancet Oncol,2014,383(9911):31-39.
17 Wilke H,Muro K,Van Cutsem E,et al.Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(RAINBOW):a double-blind,randomised phase 3 trial[J].Lancet Gastroenterol Hepatol,2014,15(11):1224-1235.
18 Xu RH,Zhang Y,Pan H,et al.Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma(RAINBOW-Asia):a randomised,multicentre,double-blind,phase 3 trial[J].Lancet Gastroenterol Hepatol,2021,6(12):1015-1024.
19 Vogl UM,Vormittag L,Winkler T,et al.Ramucirumab plus paclitaxel or FOLFIRI in platinum-refractory advanced or metastatic gastric or gastroesophageal junction adenocarcinoma-experience at two centres[J].J Gastrointest Oncol,2020,11(2):366-375.
20 Longo F,Jorge M,Yaya R,et al.Real-life use of ramucirumab in gastric cancer in Spain:the RAMIS study[J].Future Oncol,2021,17(14):1777-1791.
21 Castelo-Branco L,Pellat A,Martins-Branco D,et al.ESMO guidance for reporting oncology real-world evidence(GROW)[J].Ann Oncol,2023,34(12):1097-1112.
22 Eisenhauer EA,Therasse P,Bogaerts J,et al.New response evaluation criteria in solid tumours:revised RECIST guideline(version 1.1)[J].Eur J Cancer,2009,45(2):228-247.
23 Di Bartolomeo M,Niger M,Tirino G,et al.Ramucirumab as second-line therapy in metastatic gastric cancer:real-world data from the RAMoss Study[J].Target Oncol,2018,13(2):227-234.
24 Paulson AS,Hess LM,Liepa AM,et al.Ramucirumab for the treatment of patients with gastric or gastroesophageal junction cancer in community oncology practices[J].Gastric Cancer,2018,21(5):831-844.
25 Jung M,Ryu MH,Oh DY,et al.Efficacy and tolerability of ramucirumab monotherapy or in combination with paclitaxel in gastric cancer patients from the Expanded Access Program Cohort by the Korean Cancer Study Group(KCSG)[J].Gastric Cancer,2018,21(5):819-830.
26 Chen Y,Katayose T,Nagaoka S,et al.A post-marketing observational study of ramucirumab in patients with gastric cancer in Japan[J].Gastric Cancer,2021,24(6):1320-1329.
27 Herbst RS,Arkenau HT,Santana-Davila R,et al.Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer,gastro-oesophageal cancer,or urothelial carcinomas(JVDF):a multicohort,non-randomised,open-label,phase 1a/b trial[J].Lancet Oncol,2019,20(8):1109-1123.
28 He Y,Su Y,Zeng J,et al.Cancer-specific survival after diagnosis in men versus women:A pan-cancer analysis[J].MedComm(2020),2022,3(3):e145.

[1]	张宝综述, 郑志超校审. 进展期胃癌淋巴结清扫研究进展[J]. 实用肿瘤学杂志, 2019, 33(1): 78-81.
[2]	张锡,陈力,薛英威. 外周血中CEA和CA19-9的表达水平在进展期胃癌中的预后价值[J]. 实用肿瘤学杂志, 2017, 31(4): 342-347.
[3]	陈力, 张玉新, 左艳娇, 马菲, 宋洪江, 薛英威. SOX和XELOX在进展期胃癌新辅助化疗中的临床疗效比较[J]. 实用肿瘤学杂志, 2017, 31(1): 23-30.
[4]	许亚晔, 陈学发, 李秀娟, 周振寿. 螺旋CT扫描对进展期胃癌浸润深度的研究[J]. 实用肿瘤学杂志, 2012, 26(2): 146-149.
[5]	邱岩;罗娅红;于韬;李森. 应用低场MRI平扫评价进展期胃癌的胃壁及胃周浸润[J]. 实用肿瘤学杂志, 2008, 22(01): 32-34.
[6]	谷小虎;赵宜良. FOLFOX方案行胃癌新辅助化疗38例疗效观察[J]. 实用肿瘤学杂志, 2006, 20(06): 538-540.
[7]	王莉;俞春江;耿敬姝. 缺氧诱导因子-1α、VEGF在进展期胃癌中的表达及意义[J]. 实用肿瘤学杂志, 2005, 19(05): 337-340.
[8]	邱岩;于韬;罗娅红. 螺旋CT增强扫描对进展期胃癌胃周淋巴结转移的研究[J]. 实用肿瘤学杂志, 2004, 18(06): 449-451.
[9]	胡民主. 进展期胃癌术中及术后两周腹腔抗癌药物温热治疗分析[J]. 实用肿瘤学杂志, 2003, 17(02): 156-157.
[10]	张小龙;姜立华. 33例进展期胃癌D4手术的应用分析[J]. 实用肿瘤学杂志, 2002, 16(01): 34-35.
[11]	杨宇红;赵娟. 进展期胃癌组织氧化与抗氧化代谢特点的初步分析[J]. 实用肿瘤学杂志, 2001, 15(03): 171-172.

雷莫西尤单抗在进展期胃癌/胃食管交界部癌患者中的疗效与安全性评估:一项回顾性观察性研究

Evaluation of the efficacy and safety of ramucirumab in patients with advanced gastric cancer or gastroesophageal junction cancer:A retrospective observational study

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 11

编辑推荐

Metrics

本文评价