AbstractBackgroundThe efficacy of FOLFIRI plus an antiangiogenesis biologic agent as 2nd line therapy for metastatic colorectal adenocarcinoma is limited. TAS-102 is a novel oral antimetabolite with a distinct mechanism of action from fluoropyrimidines. We evaluated the antitumour efficacy of TAS-102, irinotecan and bevacizumab in patients with pre-treated, advanced colorectal adenocarcinoma in a multicenter, phase II, single-arm study.MethodsPatients with advanced colorectal adenocarcinoma who had progressed after oxaliplatin and fluoropyrimidine and were eligible for treatment with bevacizumab were treated with irinotecan, bevacizumab, and TAS-102 in 28-day cycles.

摘要背景FOLFIRI联合抗血管生成生物制剂作为转移性结直肠癌的二线治疗方法的疗效有限。TAS-102是一种新型口服抗代谢物，具有与氟嘧啶不同的作用机制。我们在一项多中心II期单臂研究中评估了TAS-102，伊立替康和贝伐单抗对预处理的晚期结直肠腺癌患者的抗肿瘤疗效。方法奥沙利铂和氟嘧啶治疗后进展并符合贝伐单抗治疗条件的晚期结直肠腺癌患者在28天的周期内接受伊立替康，贝伐单抗和TAS-102治疗。

The primary endpoint was progression-free survival (PFS).ResultsWe enrolled 35 evaluable patients. The study was positive. The median PFS was 7.9 (90% CI 6.2–11.8) months (vs. 6 months in historical control, p = 0.018). The median overall survival was 16.5 (90% CI 9.8–17.5) months. Sixty-seven per cent of patients experienced grade 3 or higher treatment-related adverse events.

主要终点是无进展生存期（PFS）。结果我们招募了35名可评估患者。这项研究是积极的。中位PFS为7.9（90%可信区间为6.2-11.8）个月（历史对照组为6个月，p=0.018）。中位总生存期为16.5（90%可信区间为9.8-17.5）个月。67%的患者经历了3级或更高级别的治疗相关不良事件。

The most common toxicities were hematological (neutropenia) and gastrointestinal (diarrhoea, nausea, and vomiting).ConclusionsIrinotecan, TAS-102 and bevacizumab is an active 2nd line therapy for patients with metastatic colorectal adenocarcinoma. Neutropenia is common and can affect dose density/intensity mandating use of G-CSF.

最常见的毒性是血液学（中性粒细胞减少症）和胃肠道（腹泻，恶心和呕吐）。结论sirinotecan、TAS-102和贝伐单抗是转移性结直肠腺癌患者的有效二线治疗方法。中性粒细胞减少症很常见，可能会影响剂量密度/强度，从而强制使用G-CSF。

A randomized study versus standard-of-care therapy is warranted.Clinical trial registrationClinicalTrials.gov NCT04109924..

有必要进行随机研究与标准护理治疗。临床试验注册clinicaltrials.gov NCT04109924。。

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Fig. 1: CONSORT Diagram.Fig. 2: Survival Outcomes.Fig. 3: Antitumor Efficacy.

图1：CONSORT图。图2：生存结果。图3：抗肿瘤功效。

Data availability

数据可用性

De-identified clinical data will be available upon request to the corresponding author. The raw RNA sequencing data can be accessed from https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275628.

取消识别的临床数据将根据相应作者的要求提供。原始RNA测序数据可以从https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275628.

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Download referencesAcknowledgementsTAS-102 was provided for free by Taiho Oncology. This work was partially supported by the National Cancer Institute (NCI) grants R37CA282430 to Dr. Christos Fountzilas and P30CA016056 involving the use of Roswell Park Comprehensive Cancer Center’s Biostatistics and Bioinformatics Shared Resource, Genomics Shared Resource, and the Pathology Network Shared Resource.

下载参考文献致谢TAS-102由泰和肿瘤学免费提供。这项工作得到了国家癌症研究所（NCI）的部分支持，将R37CA282430授予Christos Fountzilas博士和P30CA016056，涉及使用罗斯威尔公园综合癌症中心的生物统计学和生物信息学共享资源，基因组学共享资源和病理学网络共享资源。

The initial results of this study were presented in the American Society of Clinical Oncology 2023 Annual Meeting (Abstract 3590, Poster 290).FundingThis study was funded by the National Comprehensive Cancer Network Oncology Research Program through a grant provided by Taiho Oncology. The funder had no role in the design or interpretation of study results.Author informationAuthors and AffiliationsRutgers Cancer Institute of New Jersey, New Brunswick, NJ, USAPatrick M.

这项研究的初步结果发表在美国临床肿瘤学会2023年会上（摘要3590，海报290）。资助该研究由国家综合癌症网络肿瘤学研究计划通过泰和肿瘤学提供的资助资助。资助者在研究结果的设计或解释中没有任何作用。作者信息作者和附属机构新泽西州新泽西州新泽西州拉特格斯癌症研究所，USAPrick M。

Boland & Howard S. HochsterRoswell Park Comprehensive Cancer Center, Elm & Carlton St, Buffalo, NY, USASarbajit Mukherjee, Renuka V. Iyer, Andrei Bakin, Jianxin Wang, Sarah Chatley, Beth Cahill, Deepak Vadehra, Kristopher Attwood & Christos FountzilasMoffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, USAIman ImaniradFox Chase Cancer Center, Philadelphia, PA, USANamrata VijayvergiaMonmouth Hematology Oncology, RWJBarnanas Health, West Long Branch, NJ, USASeth D.

Boland＆Howard S.HochsterRoswell Park综合癌症中心，纽约州布法罗Elm＆Carlton街，USASarbajit Mukherjee，Renuka V.Iyer，Andrei Bakin，Jianxin Wang，Sarah Chatley，Beth Cahill，Deepak Vadehra，Kristopher Attwood＆Christos FountzilasMoffitt癌症中心，12902 USF Magnolia Drive，Tampa，FL，USAIman ImaniradFox Chase癌症中心，宾夕法尼亚州费城，USANamrata VijayvergiaMonmouth血液肿瘤学，RWJBarnanas Health，West Long Branch，NJ，USASETSET小时。

CohenProgram in Women’s Oncology, Women & Infants Hospital, Brown University, Providence, RI, USAMedhavi GuptaAuthorsPatrick M. BolandView author publicationsYou can also search for this author in.

布朗大学妇女与婴儿医院妇女肿瘤学CohenProgram，普罗维登斯，RI，USAMedhavi GUPTAAuthorsPatrickM.BolandView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsPatrick Boland - conceptualization, formal analysis, funding acquisition, data curation, methodology, project administration, and writing (review and editing), Sarbajit Mukherjee - data curation, and writing (review and editing), Iman Imanirad - project administration, data curation, and writing (review and editing), Namrata Vijayvergia project administration, data curation, and writing (review and editing), Seth Cohen - data curation, and writing (review and editing), Medhavi Gupta - methodology, and writing (review and editing), Renuka Iyer - data curation, and writing (review and editing), Andrei Bakin - formal analysis, and writing (review and editing), Jianxin Wang - formal analysis, data curation, methodology, and writing (review and editing), Sarah Chatley - data curation, and writing (review and editing), Beth Cahill - data curation, and writing (review and editing), Deepak Vadehra - data curation, and writing (review and editing), Kristopher Attwood - formal analysis, data curation, methodology, and writing (review and editing), Howard Hochster - data curation, and writing (review and editing), Christos Fountzilas - formal analysis, funding acquisition, data curation, methodology, project administration, and writing (original draft, review and editing).Corresponding authorCorrespondence to.

PubMed谷歌学术贡献Spatrick Boland-概念化，正式分析，资金获取，数据管理，方法论，项目管理和写作（审查和编辑），Sarbajit Mukherjee-数据管理和写作（审查和编辑），Iman Imanirad-项目管理，数据管理和写作（审查和编辑），Namrata Vijayvergia项目管理，数据管理和写作（审查和编辑），Seth Cohen-数据管理和写作（审查和编辑），Medhavi Gupta-方法论和写作（审查和编辑），Renuka Iyer-数据管理和写作（审查和编辑）），安德烈·巴金（Andrei Bakin）-形式分析和写作（评论和编辑），王建新（Jianxin Wang）-形式分析，数据管理，方法论和写作（评论和编辑），莎拉·查特利（Sarah Chatley）-数据管理和写作（评论和编辑），贝思·卡希尔（Beth Cahill）-数据管理和写作（评论和编辑），迪帕克·瓦德拉（Deepak Vadehra）-数据管理和写作（评论和编辑），克里斯托弗·阿特伍德（Kristopher Attwood）——正式分析、数据管理、方法论和写作（审查和编辑），霍华德·霍克斯特（Howard Hochster）——数据管理和写作（审查和编辑），克里斯托斯·丰齐拉斯（Christos Fountzilas）——正式分析、资金获取、数据管理、方法论、项目管理和写作（原稿、审查和编辑）。对应作者对应。

Christos Fountzilas.Ethics declarations

克里斯托斯·方齐拉斯。道德宣言

Competing interests

相互竞争的利益

Dr. Christos Fountzilas has research support for this clinical trial from the National Comprehensive Cancer Network Oncology Research Program (paid to the institute). He has research support from the National Comprehensive Cancer Network Foundation, Taiho Oncology, Pfizer Inc, and Merck Sharp & Dohme Corp (paid to the institute) unrelated to this study.

Christos Fountzilas博士从国家综合癌症网络肿瘤学研究计划（支付给研究所）获得了这项临床试验的研究支持。他得到了与本研究无关的国家综合癌症网络基金会，太和肿瘤学，辉瑞公司和默克制药公司（支付给该研究所）的研究支持。

Dr. Sarbajit Mukherjee has received research funding from Ipsen Biopharmaceuticals (paid to the institute) unrelated to this study. Dr. Iman Imanirad has received advisory board compensation from Eisai Co, Ltd, unrelated to this study..

Sarbajit Mukherjee博士获得了与本研究无关的Ipsen Biopharmaceuticals（支付给该研究所）的研究资金。伊曼·伊曼尼拉德博士从卫材株式会社获得了咨询委员会的报酬，与本研究无关。。

Ethics approval and consent to participate

道德批准和同意参与

The study was conducted according to the Declaration of Helsinki principles and approved by the Institutional Review Boards (IRB) from all participating institutions (Roswell Park Comprehensive Cancer Center, Rutgers Cancer Institute of New Jersey, Moffitt Cancer Center, and Fox Chase Comprehensive Cancer Center).

这项研究是根据赫尔辛基宣言原则进行的，并得到了所有参与机构（罗斯威尔公园综合癌症中心，新泽西州罗格斯癌症研究所，莫菲特癌症中心和福克斯蔡斯综合癌症中心）的机构审查委员会（IRB）的批准。

All patients provided informed consent prior to study participation. All patients providing tumor samples for whole transcriptome sequencing (de-identified Roswell Park IRB-approved protocols BDR 155422 and BDR 151721) had provided universal informed consent for use of tumor samples in research..

所有患者在参与研究之前都提供了知情同意书。所有提供肿瘤样本进行全转录组测序的患者（未经鉴定的Roswell Park IRB批准的方案BDR 155422和BDR 151721）均已提供了在研究中使用肿瘤样本的普遍知情同意书。。

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Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充材料权利和许可Pringer Nature或其许可方（例如协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有专有权；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文Boland，P.M.，Mukherjee，S.，Imanirad，I。

et al. TAS-102, Irinotecan, and bevacizumab in pre-treated metastatic colorectal cancer (TABAsCO), a phase II clinical trial..

TAS-102、伊立替康和贝伐单抗治疗转移性结直肠癌（TABAsCO）的II期临床试验。。

Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02845-xDownload citationReceived: 04 May 2024Revised: 17 August 2024Accepted: 28 August 2024Published: 07 September 2024DOI: https://doi.org/10.1038/s41416-024-02845-xShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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