Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study

医学 吉西他滨 临床终点 养生 内科学 实体瘤疗效评价标准 进行性疾病 外科 肿瘤科 胃肠病学 癌症 化疗 临床试验
作者
Milind Javle,Sameek Roychowdhury,Robin Kate Kelley,Saeed Sadeghi,Teresa Macarulla,Karl Heinz Weiss,Dirk Waldschmidt,Lipika Goyal,Ivan Borbath,Anthony B. El-Khoueiry,Mitesh J. Borad,Wei Peng Yong,Philip A. Philip,Michael Bitzer,S. Tanasanvimon,Li Ai,Amit Pande,Harris S. Soifer,Stacie Peacock Shepherd,Susan Moran,Andrew X. Zhu,Tanios Bekaii‐Saab,Ghassan K. Abou‐Alfa
出处
期刊:The Lancet Gastroenterology & Hepatology [Elsevier]
卷期号:6 (10): 803-815 被引量:263
标识
DOI:10.1016/s2468-1253(21)00196-5
摘要

Background Treatment options are sparse for patients with advanced cholangiocarcinoma after progression on first-line gemcitabine-based therapy. FGFR2 fusions or rearrangements occur in 10–16% of patients with intrahepatic cholangiocarcinoma. Infigratinib is a selective, ATP-competitive inhibitor of fibroblast growth factor receptors. We aimed to evaluate the antitumour activity of infigratinib in patients with locally advanced or metastatic cholangiocarcinoma, FGFR2 alterations, and previous gemcitabine-based treatment. Methods This multicentre, open-label, single-arm, phase 2 study recruited patients from 18 academic centres and hospitals in the USA, Belgium, Spain, Germany, Singapore, Taiwan, and Thailand. Eligible participants were aged 18 years or older, had histologically or cytologically confirmed, locally advanced or metastatic cholangiocarcinoma and FGFR2 fusions or rearrangements, and were previously treated with at least one gemcitabine-containing regimen. Patients received 125 mg of oral infigratinib once daily for 21 days of 28-day cycles until disease progression, intolerance, withdrawal of consent, or death. Radiological tumour evaluation was done at baseline and every 8 weeks until disease progression via CT or MRI of the chest, abdomen, and pelvis. The primary endpoint was objective response rate, defined as the proportion of patients with a best overall response of a confirmed complete or partial response, as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors, version 1.1. The primary outcome and safety were analysed in the full analysis set, which comprised all patients who received at least one dose of infigratinib. This trial is registered with ClinicalTrials.gov, NCT02150967, and is ongoing. Findings Between June 23, 2014, and March 31, 2020, 122 patients were enrolled into our study, of whom 108 with FGFR2 fusions or rearrangements received at least one dose of infigratinib and comprised the full analysis set. After a median follow-up of 10·6 months (IQR 6·2–15·6), the BICR-assessed objective response rate was 23·1% (95% CI 15·6–32·2; 25 of 108 patients), with one confirmed complete response in a patient who only had non-target lesions identified at baseline and 24 partial responses. The most common treatment-emergent adverse events of any grade were hyperphosphataemia (n=83), stomatitis (n=59), fatigue (n=43), and alopecia (n=41). The most common ocular toxicity was dry eyes (n=37). Central serous retinopathy-like and retinal pigment epithelial detachment-like events occurred in 18 (17%) patients, of which ten (9%) were grade 1, seven (6%) were grade 2, and one (1%) was grade 3. There were no treatment-related deaths. Interpretation Infigratinib has promising clinical activity and a manageable adverse event profile in previously treated patients with locally advanced or metastatic cholangiocarcinoma harbouring FGFR2 gene fusions or rearrangements, and so represents a potential new therapeutic option in this setting. Funding QED Therapeutics and Novartis.
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
大幅提高文件上传限制,最高150M (2024-4-1)

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
pp完成签到,获得积分10
2秒前
2秒前
儒雅沛凝完成签到 ,获得积分10
3秒前
小小沙完成签到 ,获得积分10
4秒前
4秒前
打打应助fighting采纳,获得10
4秒前
坦率的从波完成签到 ,获得积分10
5秒前
小七完成签到,获得积分10
8秒前
大_pan完成签到,获得积分10
9秒前
子车谷波完成签到,获得积分10
9秒前
腾腾完成签到 ,获得积分10
9秒前
儒雅的焦完成签到,获得积分10
10秒前
11秒前
13秒前
一一完成签到,获得积分10
13秒前
14秒前
14秒前
chawenxian2025完成签到,获得积分10
14秒前
15秒前
蔡夜安完成签到,获得积分10
16秒前
Apr9810h完成签到 ,获得积分10
17秒前
奥里给发布了新的文献求助10
17秒前
爱笑的冷风完成签到 ,获得积分10
17秒前
ajiduo完成签到 ,获得积分10
17秒前
火星上的小蚂蚁完成签到,获得积分0
18秒前
fighting发布了新的文献求助10
18秒前
飞翔的荷兰人完成签到,获得积分10
19秒前
19秒前
高手如林完成签到,获得积分10
20秒前
顺利秋灵发布了新的文献求助10
21秒前
白日梦小说家完成签到 ,获得积分10
22秒前
科研小笨猪完成签到,获得积分10
23秒前
24秒前
含蓄的易蓉完成签到,获得积分10
25秒前
山大王yoyo完成签到,获得积分10
25秒前
Carrie完成签到,获得积分20
26秒前
Yyy完成签到 ,获得积分10
27秒前
小黄不慌完成签到,获得积分10
28秒前
顺利秋灵完成签到,获得积分10
28秒前
好学的X发布了新的文献求助20
28秒前
高分求助中
The ACS Guide to Scholarly Communication 2500
Microlepidoptera Palaearctica, Volumes 1 and 3 - 13 (12-Volume Set) [German] 1122
Subjective Well-Being and Life Satisfaction (第二版) 1000
The Data Economy: Tools and Applications 1000
PraxisRatgeber Mantiden., faszinierende Lauerjäger. – Buch gebraucht kaufen 700
Mantiden - Faszinierende Lauerjäger – Buch gebraucht kaufen 700
Acute Care Physical Therapy 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3095267
求助须知:如何正确求助?哪些是违规求助? 2747176
关于积分的说明 7593269
捐赠科研通 2398823
什么是DOI,文献DOI怎么找? 1272701
科研通“疑难数据库(出版商)”最低求助积分说明 615427
版权声明 598931