Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial

帕妥珠单抗 医学 曲妥珠单抗 曲妥珠单抗 多西紫杉醇 肿瘤科 内科学 卡铂 乳腺癌 新辅助治疗 养生 转移性乳腺癌 化疗 癌症 顺铂
作者
Sara A. Hurvitz,Miguel Martín,W. Fraser Symmans,Kyung Hae Jung,Chiun‐Sheng Huang,Alastair M. Thompson,Nadia Harbeck,Vicente Valero,Daniil Stroyakovskiy,Hans Wildiers,Mario Campone,Jean-François Boileau,Matthias W. Beckmann,Karen Afenjar,Rodrigo Fresco,Hans‐Joachim Helms,Jin Xu,Yvonne G. Lin,Joseph A. Sparano,Dennis J. Slamon
出处
期刊:Lancet Oncology [Elsevier BV]
卷期号:19 (1): 115-126 被引量:435
标识
DOI:10.1016/s1470-2045(17)30716-7
摘要

Background HER2-targeted treatments have improved outcomes in patients with HER2-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings; however, some patients remain at risk of relapse or death for many years after treatment of early-stage disease. Therefore, new strategies are needed. We did a phase 3 trial to assess a neoadjuvant regimen for HER2-positive breast cancer that replaces traditional systemic chemotherapy with targeted treatment. Methods We did a randomised, open-label phase 3 KRISTINE trial in 68 Translational Research In Oncology centres (hospitals and specialty cancer centres in Asia, Europe, USA, and Canada). Eligible participants were aged 18 years or older with centrally confirmed HER2-positive stage II–III operable breast cancer (>2 cm tumour size), an Eastern Cooperative Oncology Group performance status of 0–1, and a baseline left ventricular ejection fraction of at least 55% (by echocardiogram or multiple-gated acquisition scan). We randomly assigned participants (1:1) to receive either trastuzumab emtansine plus pertuzumab or docetaxel, carboplatin, and trastuzumab plus pertuzumab. We did the randomisation via an interactive response system under a permuted block randomisation scheme (block size of four), stratified by hormone receptor status, stage at diagnosis, and geographical location. Patients received six cycles (every 3 weeks) of neoadjuvant trastuzumab emtansine plus pertuzumab (trastuzumab emtansine 3·6 mg/kg; pertuzumab 840 mg loading dose, 420 mg maintenance doses) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (docetaxel 75 mg/m2; carboplatin area under the concentration–time curve 6 mg/mL × min; trastuzumab 8 mg/kg loading dose, 6 mg/kg maintenance doses) plus pertuzumab [same dosing as in the other group]). All treatments were administered intravenously. The primary objective was to compare the number of patients who achieved a pathological complete response (ypT0/is, ypN0), between groups in the intention-to-treat population (two-sided assessment), based on local evaluation of tumour samples taken at breast cancer surgery done between 14 days and 6 weeks after completion of neoadjuvant therapy. Safety was analysed in patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02131064, and follow-up of the adjuvant phase is ongoing. Findings Between June 25, 2014, and June 15, 2015, we randomly assigned 444 patients to neoadjuvant treatment with trastuzumab emtansine plus pertuzumab (n=223) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (n=221). A pathological complete response was achieved by 99 (44·4%) of 223 patients in the trastuzumab emtansine plus pertuzumab group and 123 (55·7%) of 221 patients in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group (absolute difference −11·3 percentage points, 95% CI −20·5 to −2·0; p=0·016). During neoadjuvant treatment, compared with patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab, fewer patients receiving trastuzumab emtansine plus pertuzumab had a grade 3–4 adverse event (29 [13%] of 223 vs 141 [64%] of 219) or a serious adverse event (11 [5%] of 223 vs 63 [29%] of 219). The most common grade 3–4 adverse events in the trastuzumab emtansine plus pertuzumab group were decreased platelet count (three [1%] of 223 patients vs 11 [5%] of 219 with docetaxel, carboplatin, and trastuzumab plus pertuzumab), fatigue (three [1%] vs seven [3%]), alanine aminotransferase increase (three [1%] vs four [2%]), and hypokalaemia (three [1%] vs five [2%]). The most common grade 3–4 adverse events in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group were neutropenia (55 [25%] of 219 vs one [<1%] of 223 with trastuzumab emtansine plus pertuzumab), diarrhoea (33 [15%] vs 2 [<1%]), and febrile neutropenia (33 [15%] vs 0). No deaths were reported during neoadjuvant treatment. Interpretation Traditional neoadjuvant systemic chemotherapy plus dual HER2-targeted blockade (docetaxel, carboplatin, and trastuzumab plus pertuzumab) resulted in significantly more patients achieving a pathological complete response than HER2-targeted chemotherapy plus HER2-targeted blockade (trastuzumab emtansine plus pertuzumab); however, numerically more grade 3–4 and serious adverse events occurred in the chemotherapy plus trastuzumab and pertuzumab group. Further efforts to improve the efficacy of chemotherapy without imparting more toxicity are warranted. Funding F Hoffmann-La Roche and Genentech.
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
有魅力的小蜜蜂完成签到,获得积分10
1秒前
慕青应助lizhaonian采纳,获得10
1秒前
耍酷的傲霜完成签到,获得积分10
2秒前
善学以致用应助jjsun采纳,获得10
3秒前
EED应助文件撤销了驳回
3秒前
小蘑菇应助年轻的烨华采纳,获得10
4秒前
4秒前
zzz发布了新的文献求助10
5秒前
研友_Zzrx6Z完成签到,获得积分10
6秒前
6秒前
8秒前
8秒前
汉堡包应助NOTHING采纳,获得10
8秒前
SYLH应助科研通管家采纳,获得50
8秒前
quhayley应助科研通管家采纳,获得10
8秒前
爆米花应助科研通管家采纳,获得10
8秒前
坦率的匪应助科研通管家采纳,获得10
9秒前
田様应助科研通管家采纳,获得10
9秒前
SYLH应助科研通管家采纳,获得50
9秒前
orixero应助科研通管家采纳,获得10
9秒前
SYLH应助科研通管家采纳,获得50
9秒前
思源应助科研通管家采纳,获得10
9秒前
9秒前
隐形曼青应助科研通管家采纳,获得10
9秒前
czh应助科研通管家采纳,获得10
9秒前
赘婿应助科研通管家采纳,获得10
9秒前
华仔应助科研通管家采纳,获得10
9秒前
科研通AI2S应助科研通管家采纳,获得10
9秒前
10秒前
SYLH应助科研通管家采纳,获得50
10秒前
大模型应助科研通管家采纳,获得10
10秒前
10秒前
斯文败类应助Keyl采纳,获得10
10秒前
褪黑素应助科研通管家采纳,获得10
10秒前
完美世界应助科研通管家采纳,获得10
10秒前
10秒前
10秒前
10秒前
10秒前
10秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
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 3988732
求助须知:如何正确求助?哪些是违规求助? 3531027
关于积分的说明 11252281
捐赠科研通 3269732
什么是DOI,文献DOI怎么找? 1804764
邀请新用户注册赠送积分活动 881869
科研通“疑难数据库(出版商)”最低求助积分说明 809021