Efficacy and Safety of Single-Agent Pertuzumab, a Human Epidermal Receptor Dimerization Inhibitor, in Patients with Non–Small Cell Lung Cancer

帕妥珠单抗 医学 肺癌 临床终点 内科学 标准摄取值 药效学 肿瘤科 置信区间 癌症 正电子发射断层摄影术 胃肠病学 核医学 临床试验 曲妥珠单抗 药代动力学 乳腺癌
作者
Roy S. Herbst,Angela M. Davies,Ronald B. Natale,Thao P. Dang,Joan H. Schiller,Linda L. Garland,Vincent A. Miller,David S. Mendelson,Annick D. Van den Abbeele,Yulia V. Melenevsky,D.J. de Vries,David A. Eberhard,Benjamin Lyons,Stuart Lutzker,Bruce E. Johnson
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:13 (20): 6175-6181 被引量:91
标识
DOI:10.1158/1078-0432.ccr-07-0460
摘要

Abstract Purpose: Pertuzumab, a first-in-class human epidermal receptor 2 (HER2) dimerization inhibitor, is a humanized monoclonal anti-HER2 antibody that binds HER2's dimerization domain and inhibits HER2 signaling. Based on supporting preclinical studies, we undertook a Phase II trial of pertuzumab in patients with recurrent non–small cell lung cancer (NSCLC). Experimental Design: Patients with previously treated NSCLC accessible for core biopsy and naive to HER pathway inhibitors were treated with pertuzumab i.v. once every 3 weeks. Tumor assessments were done at 6 and 12 weeks and then every 3 months thereafter. The primary efficacy end point was overall response rate by Response Evaluation Criteria in Solid Tumors. Measurement of tumor glucose metabolism (SUVmax) by F-18-fluorodeoxyglucose positron emission tomography was used as an exploratory pharmacodynamic marker of drug activity. Results: Of 43 patients treated with pertuzumab, no responses were seen; 18 of 43 (41.9%) and 9 of 43 (20.9%) patients had stable disease at 6 and 12 weeks, respectively. The median and 3-month progression-free survival rates (PFS) were 6.1 weeks (95% confidence interval, 5.3-11.3 weeks) and 28.4% (95% confidence interval, 14.4-44.2%), respectively. Of 22 patients who underwent F-18-fluorodeoxyglucose positron emission tomography, six (27.3%) had a metabolic response to pertuzumab as evidenced by decreased SUVmax. These patients had prolonged PFS (HR = 0.11, log-rank P value = 0.018) compared with the 16 patients who had no metabolic response. Four patients (9.3%) experienced a grade 3/grade 4 adverse event judged related to pertuzumab; none exhibited grade 3/grade 4 cardiac toxicity. Conclusions: Pertuzumab is well tolerated as monotherapy. Pharmacodynamic activity correlated with prolonged PFS was detected in a moderate percentage of patients (27.3%). Further clinical development of pertuzumab should focus on rational combinations of pertuzumab with other drugs active in NSCLC.
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
刚刚
义气妙之完成签到,获得积分10
1秒前
田様应助小灯采纳,获得10
2秒前
2秒前
3秒前
研友_LOaymZ发布了新的文献求助10
3秒前
专注半烟发布了新的文献求助10
3秒前
3秒前
4秒前
5秒前
大仙生发布了新的文献求助10
6秒前
7秒前
shinysparrow应助邢夏之采纳,获得20
7秒前
123发布了新的文献求助10
9秒前
9秒前
orixero应助觅桃乌龙采纳,获得10
9秒前
研友_VZG7GZ应助火焰向上采纳,获得10
9秒前
9秒前
10秒前
隐形曼青应助Hi采纳,获得10
12秒前
李爱国应助项初蝶采纳,获得10
13秒前
14秒前
15秒前
15秒前
15秒前
16秒前
lyx完成签到,获得积分10
16秒前
田様应助123采纳,获得10
18秒前
llls完成签到 ,获得积分10
19秒前
张馨发布了新的文献求助10
19秒前
洪亮完成签到,获得积分0
20秒前
vagabond发布了新的文献求助10
20秒前
SciGPT应助123采纳,获得10
20秒前
火焰向上发布了新的文献求助10
21秒前
西门博超发布了新的文献求助10
21秒前
啵子完成签到,获得积分10
22秒前
华仔应助flamezzz采纳,获得10
22秒前
可耐的康发布了新的文献求助10
22秒前
23秒前
Lucas应助小灯采纳,获得10
23秒前
高分求助中
Teaching Social and Emotional Learning in Physical Education 900
Plesiosaur extinction cycles; events that mark the beginning, middle and end of the Cretaceous 800
Recherches Ethnographiques sue les Yao dans la Chine du Sud 500
Two-sample Mendelian randomization analysis reveals causal relationships between blood lipids and venous thromboembolism 500
Chinese-English Translation Lexicon Version 3.0 500
[Lambert-Eaton syndrome without calcium channel autoantibodies] 440
Wisdom, Gods and Literature Studies in Assyriology in Honour of W. G. Lambert 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 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 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2389575
求助须知:如何正确求助?哪些是违规求助? 2095545
关于积分的说明 5277858
捐赠科研通 1822726
什么是DOI,文献DOI怎么找? 909073
版权声明 559537
科研通“疑难数据库(出版商)”最低求助积分说明 485774