一项评估雷莫西尤单抗联合mFOLFOX-6作为转移性结直肠癌一线治疗的安全性和疗效的开放标签II期研究。

An open-label phase II study evaluating the safety and efficacy of ramucirumab combined with mFOLFOX-6 as first-line therapy for metastatic colorectal cancer.

作者信息

Garcia-Carbonero Rocio, Rivera Fernando, Maurel Joan, Ayoub Jean-Pierre M, Moore Malcolm J, Cervantes Andres, Asmis Timothy R, Schwartz Jonathan D, Nasroulah Federico, Ballal Shaila, Tabernero Josep

机构信息

Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla (center affiliated with the Red Temática de Investigación Cooperativa en Cancer, Instituto Carlos III, Spanish Ministry of Science and Innovation), Sevilla, Spain;

出版信息

Oncologist. 2014 Apr;19(4):350-1. doi: 10.1634/theoncologist.2014-0028. Epub 2014 Mar 27.

DOI:10.1634/theoncologist.2014-0028

PMID:24674871

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3983832/

Abstract

BACKGROUND

Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) are believed to mediate angiogenesis in colorectal cancer (CRC). Ramucirumab (RAM; IMC-1121B) is a human IgG1 monoclonal antibody that inhibits VEGF ligand binding to VEGFR-2, inhibiting VEGFR-2 activation and signaling.

METHODS

Patients with metastatic CRC, Eastern Cooperative Oncology Group performance status 0-1, and adequate organ function who had not received chemotherapy for metastatic disease received RAM and the modified FOLFOX-6 regimen every 2 weeks. Endpoints included progression-free survival (PFS), objective response rate, overall survival, and safety. The sample size was based on a potentially improved median PFS from 8 months to 11 months.

RESULTS

Forty-eight patients received therapy. Median PFS was 11.5 months (95% confidence interval [CI]: 8.6-13.1 months). The objective response rate was 58.3% (95% CI: 43.21-72.39). The disease control rate (complete or partial response plus stable disease) was 93.8% (95% CI: 82.8-98.7). Median overall survival was 20.4 months (95% CI: 18.5-25.1 months). The most frequent grade 3-4 adverse events included neutropenia (grade 3: 33.3%; grade 4: 8.3%), hypertension (grade 3: 16.7%), and neuropathy (grade 3: 12.5%). Two patients died during the study due to myocardial infarction and cardiopulmonary arrest.

CONCLUSION

RAM may enhance the efficacy of modified FOLFOX-6 chemotherapy with an acceptable safety profile in metastatic CRC.

摘要

背景

血管内皮生长因子（VEGF）和VEGF受体2（VEGFR - 2）被认为在结直肠癌（CRC）中介导血管生成。雷莫西尤单抗（RAM；IMC - 1121B）是一种人IgG1单克隆抗体，可抑制VEGF配体与VEGFR - 2结合，抑制VEGFR - 2激活和信号传导。

方法

转移性CRC患者，东部肿瘤协作组体能状态为0 - 1，且器官功能良好，未接受过转移性疾病化疗，每2周接受RAM和改良的FOLFOX - 6方案治疗。终点包括无进展生存期（PFS）、客观缓解率、总生存期和安全性。样本量基于中位PFS可能从8个月提高到11个月。

结果

48例患者接受治疗。中位PFS为11.5个月（95%置信区间[CI]：8.6 - 13.1个月）。客观缓解率为58.3%（95% CI：43.21 - 72.39）。疾病控制率（完全或部分缓解加疾病稳定）为93.8%（95% CI：82.8 - 98.7）。中位总生存期为20.4个月（95% CI：18.5 - 25.1个月）。最常见的3 - 4级不良事件包括中性粒细胞减少（3级：33.3%；4级：8.3%）、高血压（3级：16.7%）和神经病变（3级：12.5%）。两名患者在研究期间因心肌梗死和心肺骤停死亡。