Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study

医学 紫杉烷 肿瘤科 临床终点 内科学 曲妥珠单抗 养生 耐受性 多西紫杉醇 曲妥珠单抗 卡培他滨 人口 癌症 转移性乳腺癌 外科 乳腺癌 临床试验 不利影响 结直肠癌 环境卫生
作者
Peter Thuss‐Patience,Manish A. Shah,Atsushi Ohtsu,Eric Van Cutsem,Jaffer A. Ajani,Hugo R. Castro,Wasat Mansoor,Hyun Cheol Chung,G. Bodoky,Kohei Shitara,Gail D. Lewis Phillips,T. van der Horst,Marie-Laurence Harle-Yge,Betsy Althaus,Yoon‐Koo Kang
出处
期刊:Lancet Oncology [Elsevier BV]
卷期号:18 (5): 640-653 被引量:471
标识
DOI:10.1016/s1470-2045(17)30111-0
摘要

Background Although trastuzumab plus chemotherapy is the standard of care for first-line treatment of HER2-positive advanced gastric cancer, there is no established therapy in the second-line setting. In GATSBY, we examined the efficacy and tolerability of trastuzumab emtansine in patients previously treated for HER2-positive advanced gastric cancer (unresectable, locally advanced, or metastatic gastric cancer, including adenocarcinoma of the gastro-oesophageal junction). Methods This is the final analysis from GATSBY, a randomised, open-label, adaptive, phase 2/3 study, done at 107 centres (28 countries worldwide). Eligible patients had HER2-positive advanced gastric cancer and progressed during or after first-line therapy. In stage one of the trial, patients were randomly assigned to treatment groups (2:2:1) to receive intravenous trastuzumab emtansine (3·6 mg/kg every 3 weeks or 2·4 mg/kg weekly) or physician's choice of a taxane (intravenous docetaxel 75 mg/m2 every 3 weeks or intravenous paclitaxel 80 mg/m2 weekly). In stage two, patients were randomly assigned to treatment groups (2:1) to receive the independent data monitoring committee (IDMC)-selected dose of trastuzumab emtansine (2·4 mg/kg weekly) or a taxane (same regimen as above). We used permuted block randomisation, stratified by world region, previous HER2-targeted therapy, and previous gastrectomy. The primary endpoint (overall survival) was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01641939. Findings Between Sept 3, 2012, and Oct 14, 2013, 70 patients were assigned to receive trastuzumab emtansine 3·6 mg/kg every 3 weeks, 75 to receive trastuzumab emtansine 2·4 mg/kg weekly, and 37 to receive a taxane in the stage 1 part of the trial. At the pre-planned interim analysis (Oct 14, 2013), the IDMC selected trastuzumab emtansine 2·4 mg/kg weekly as the dose to proceed to stage 2. By Feb 9, 2015, a further 153 patients had been randomly assigned to receive trastuzumab emtansine 2·4 mg/kg weekly and a further 80 to receive a taxane. At data cutoff, median follow-up was 17·5 months (IQR 12·1–23·0) for the trastuzumab emtansine 2·4 mg/kg weekly group and 15·4 months (9·2–18·1) in the taxane group. Median overall survival was 7·9 months (95% CI 6·7–9·5) with trastuzumab emtansine 2·4 mg/kg weekly and 8·6 months (7·1–11·2) with taxane treatment (hazard ratio 1·15, 95% CI 0·87–1·51, one-sided p=0·86). The trastuzumab emtansine 2·4 mg/kg group had lower incidences of grade 3 or more adverse events (134 [60%] of 224 patients treated with trastuzumab emtansine vs 78 [70%] of 111 patients treated with a taxane), and similar incidences of adverse events leading to death (eight [4%] vs four [4%]), serious adverse events (65 [29%] vs 31 [28%]), and adverse events leading to treatment discontinuation (31 [14%] vs 15 [14%]) than did taxane treatment. The most common grade 3 or more adverse events in the trastuzumab emtansine 2·4 mg/kg weekly group were anaemia (59 [26%]) and thrombocytopenia (25 [11%]) compared with neutropenia (43 [39%]), and anaemia (20 [18%]), in the taxane group. The most common serious adverse events were anaemia (eight [4%]), upper gastrointestinal haemorrhage (eight [4%]), pneumonia (seven [3%]), gastric haemorrhage (six [3%]), and gastrointestinal haemorrhage (five [2%]) in the trastuzumab emtansine 2·4 mg/kg weekly group compared with pneumonia (four [4%]), febrile neutropenia (four [4%]), anaemia (three [3%]), and neutropenia (three [3%]) in the taxane group. Interpretation Trastuzumab emtansine was not superior to taxane in patients with previously treated, HER2-positive advanced gastric cancer. There is still an unmet need in this patient group and therapeutic options remain limited. Funding F Hoffmann-La Roche.
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
刚刚
Suliove完成签到,获得积分10
1秒前
zys2001mezy发布了新的文献求助10
1秒前
郭一一完成签到,获得积分10
1秒前
1秒前
2秒前
明天会更美好完成签到,获得积分10
2秒前
醉眠关注了科研通微信公众号
2秒前
2秒前
3秒前
五五应助SRQ采纳,获得10
3秒前
3秒前
着慵懒时光的猫完成签到,获得积分10
3秒前
自由大叔完成签到,获得积分10
4秒前
4秒前
zhinian28发布了新的文献求助10
4秒前
JamesPei应助djbj2022采纳,获得10
4秒前
4秒前
5秒前
强健的鼠标完成签到,获得积分10
5秒前
jinghong完成签到 ,获得积分10
5秒前
5秒前
早日毕业完成签到,获得积分10
5秒前
5秒前
家伟发布了新的文献求助10
5秒前
三杠发布了新的文献求助20
6秒前
6秒前
biubiudididi发布了新的文献求助10
7秒前
开心的城发布了新的文献求助10
7秒前
李健应助Bonnie采纳,获得10
7秒前
搜集达人应助科研通管家采纳,获得10
7秒前
科目三应助科研通管家采纳,获得10
8秒前
lin应助wos采纳,获得10
8秒前
8秒前
感性的俊驰完成签到 ,获得积分10
8秒前
ll应助科研通管家采纳,获得10
8秒前
8秒前
Jasper应助科研通管家采纳,获得10
8秒前
大模型应助科研通管家采纳,获得10
8秒前
出租耳朵应助科研通管家采纳,获得10
8秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
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 3969335
求助须知:如何正确求助?哪些是违规求助? 3514162
关于积分的说明 11172430
捐赠科研通 3249456
什么是DOI,文献DOI怎么找? 1794853
邀请新用户注册赠送积分活动 875437
科研通“疑难数据库(出版商)”最低求助积分说明 804809