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

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）以及VEGF受体2（VEGFR‐2）被认为能够介导结直肠癌（CRC）的血管生成。Ramucirumab（RAM；IMC‐1121B）是人类lgG1单克隆抗体，可抑制VEGF配体与VEGFR‐2结合，阻碍VEGFR‐2激活与信号传导。 方法.入组转移性CRC患者，东部肿瘤协作组体能状态评分0 ∼ 1分，具有足够的器官功能，且既往未接受过对转移性肿瘤的化疗，这些患者入组后接受RAM和改良的FOLFOX‐6方案，每2周1次。研究终点包括无疾病进展生存期（PFS）、客观缓解率、总生存期（OS）以及安全性。预计中位PFS可能从8个月延长至11个月，在此基础上估算样本量。 结果. 48例患者接受了治疗。中位PFS为11.5个月[95%可信区间（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（完全或部分缓解以及疾病稳定）为93.8%（95% CI：82.8 ∼ 98.7）。中位OS为20.4个月（95% CI：18.5 ∼ 25.1个月）。最常发生的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%）以及神经病变（3级：12.5%）。2例患者在研究期间因心肌梗死和心肺骤停而死亡。 结论. 在转移性CRC中，RAM可能增强改良的FOLFOX‐6化疗方案的疗效，而且安全性谱可接受。The Oncologist 2014;19:350‐351