Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial

医学 吉西他滨 卡铂 内科学 化疗 转移性乳腺癌 乳腺癌 肿瘤科 三阴性乳腺癌 胃肠病学 癌症 外科 顺铂
作者
Antoinette R. Tan,Gail S. Wright,Anu Thummala,Michael Danso,Lazar Popović,Timothy Pluard,Hyo S. Han,Željko Vojnović,Nikola Vasev,Ling Ma,Donald Richards,Sharon Wilks,Dušan Milenković,Yang Zhao,Joyce Antal,Shannon R. Morris,Joyce O’Shaughnessy
出处
期刊:Lancet Oncology [Elsevier BV]
卷期号:20 (11): 1587-1601 被引量:99
标识
DOI:10.1016/s1470-2045(19)30616-3
摘要

Summary

Background

Trilaciclib is an intravenous cell-cycle inhibitor that transiently maintains immune cells and haemopoietic stem and progenitor cells in G1 arrest. By protecting the immune cells and bone marrow from chemotherapy-induced damage, trilaciclib has the potential to optimise antitumour activity while minimising myelotoxicity. We report safety and activity data for trilaciclib plus gemcitabine and carboplatin chemotherapy in patients with metastatic triple-negative breast cancer.

Methods

In this randomised, open-label, multicentre, phase 2 study, adult patients (aged ≥18 years) with evaluable, biopsy-confirmed, locally recurrent or metastatic triple-negative breast cancer who had no more than two previous lines of chemotherapy were recruited from 26 sites in the USA, three in Serbia, two in North Macedonia, one in Croatia, and one in Bulgaria; sites were academic and community hospitals. Availability of diagnostic samples of tumour tissue confirming triple-negative breast cancer was a prerequisite for enrolment. Eligible patients were randomly assigned (1:1:1) by an interactive web-response system, stratified by number of previous lines of systemic therapy and the presence of liver metastases, to receive intravenous gemcitabine 1000 mg/m2 and intravenous carboplatin (area under the concentration-time curve 2 μg × h/mL) on days 1 and 8 (group 1), gemcitabine and carboplatin plus intravenous trilaciclib 240 mg/m2 on days 1 and 8 (group 2), or gemcitabine and carboplatin on days 2 and 9 plus trilaciclib on days 1, 2, 8, and 9 (group 3) of 21-day cycles. Patients continued treatment until disease progression, unacceptable toxicity, withdrawal of consent, or discontinuation by the investigator. The primary objective was to assess the safety and tolerability of combining trilaciclib with gemcitabine and carboplatin chemotherapy. The primary endpoints were duration of severe neutropenia during cycle 1 and the occurrence of severe neutropenia during the treatment period. Overall survival was included as a key secondary endpoint. Analyses were in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with EudraCT, 2016-004466-26, and ClinicalTrials.gov, NCT02978716, and is ongoing but closed to accrual.

Findings

Between Feb 7, 2017, and May 15, 2018, 142 patients were assessed for eligibility and 102 were randomly assigned to group 1 (n=34), group 2 (n=33), or group 3 (n=35). Of all patients, 38 (37%) had received one or two lines of previous chemotherapy in the metastatic setting. Median follow-up was 8·4 months (IQR 3·8–13·6) for group 1, 12·7 months (5·5–17·4) for group 2, and 12·9 months (6·7–16·8) for group 3. Data cutoff for myelosuppression endpoints was July 30, 2018, and for antitumour activity endpoints was May 17, 2019. During cycle 1, mean duration of severe neutropenia was 0·8 day (SD 2·4) in group 1, 1·5 days (3·5) in group 2, and 1·0 day (2·6) in group 3 (group 3 vs group 1 one-sided adjusted p=0·70). Severe neutropenia occurred in nine (26%) of 34 patients in group 1, 12 (36%) of 33 patients in group 2, and eight (23%) of 35 patients in group 3 (p=0·70). Overall survival was 12·6 months (IQR 5·8–15·6) in group 1, 20·1 months (9·4–not reached) in group 2, and 17·8 months (8·8–not reached) in group 3 (group 3 vs group 1 two-sided p=0·0023). The most common treatment-emergent adverse events were anaemia (22 [73%] of 34), neutropenia (21 [70%]), and thrombocytopenia (18 [60%]) in group 1; neutropenia (27 [82%] of 33), thrombocytopenia (18 [55%]) and anaemia (17 [52%]) in group 2; and neutropenia (23 [66%] of 35), thrombocytopenia (22 [63%]), and nausea (17 [49%]) in group 3. There were no treatment-related deaths.

Interpretation

No significant differences were observed in myelosuppression endpoints with trilaciclib plus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer; however, the regimen was generally well tolerated and overall survival results were encouraging. Further studies of trilaciclib in this setting are warranted.

Funding

G1 Therapeutics.
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
仂尤完成签到,获得积分10
刚刚
剑鬼完成签到,获得积分10
1秒前
1秒前
科研小白完成签到,获得积分10
2秒前
文艺孱关注了科研通微信公众号
2秒前
QWQ完成签到,获得积分10
3秒前
哈儿的跟班完成签到,获得积分10
3秒前
4秒前
电机小学生完成签到,获得积分10
4秒前
奶黄包完成签到 ,获得积分10
5秒前
5秒前
zhenya完成签到,获得积分10
5秒前
6秒前
6秒前
暴躁的海ge完成签到,获得积分10
7秒前
7秒前
小谢完成签到,获得积分10
8秒前
从容乌完成签到 ,获得积分10
8秒前
甲乙丙丁完成签到,获得积分10
8秒前
8秒前
如意的尔蝶完成签到,获得积分10
8秒前
儒雅的菠萝吹雪完成签到,获得积分10
9秒前
AN完成签到,获得积分10
10秒前
苹果完成签到 ,获得积分10
10秒前
淡然钢笔完成签到,获得积分10
10秒前
liuyuqi完成签到,获得积分20
10秒前
碧蓝的安柏完成签到,获得积分10
10秒前
10秒前
卓头OvQ完成签到,获得积分10
10秒前
Khr1stINK完成签到,获得积分10
11秒前
暗栀发布了新的文献求助10
11秒前
酷酷阑香发布了新的文献求助10
11秒前
含蓄绿兰完成签到,获得积分10
11秒前
甲乙丙丁发布了新的文献求助10
12秒前
john完成签到,获得积分10
12秒前
12秒前
爽o发布了新的文献求助10
12秒前
En应助小马baby采纳,获得10
13秒前
臭屁大王完成签到,获得积分10
13秒前
13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
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 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 3968637
求助须知:如何正确求助?哪些是违规求助? 3513552
关于积分的说明 11168493
捐赠科研通 3248935
什么是DOI,文献DOI怎么找? 1794554
邀请新用户注册赠送积分活动 875188
科研通“疑难数据库(出版商)”最低求助积分说明 804691