Lessons learned: Ramucirumab was well tolerated in Chinese patients with advanced solid tumors, and adverse events were manageable in this study.Pharmacokinetics characteristics in Chinese patients were similar to those in other populations. Immunogenicity was not detected.No efficacy conclusion could be drawn, and further randomized studies are warranted.
Background: This single-arm, nonrandomized, open-label, dose-escalation, phase I study was designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of ramucirumab in Chinese patients with advanced solid tumors that were resistant to standard therapy or no standard therapy was available.
Methods: Dose escalation was a 3 + 3 design, with expansion in Cohorts 2 and 3 for PK. Ramucirumab was given intravenously at three different dosages: 6 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, and 8 mg/kg every 2 weeks. Safety analyses included all patients. PK, immunogenicity, and antitumor activity were also assessed.
Results: Among 28 patients treated, 2 experienced dose-limiting toxicity, possibly related to ramucirumab. No maximum tolerated dose was determined. All patients experienced at least one treatment-emergent adverse event. Grade ≥3 adverse event was reported for 53.6% (n = 15) of patients. PK analyses indicated that ramucirumab had low clearance, small volume of distribution, and long half-life in Chinese patients, as in other populations. Immunogenicity was not detected. No patient had complete/partial response, and 64.3% (n = 18) had stable disease with a median duration of 5.55 months (95% confidence interval: 3.38-7.13 months).
Conclusion: Ramucirumab appeared to be well tolerated in Chinese patients with advanced solid tumors. PK characteristics in Chinese patients were similar to those in other populations.
经验总结
• 本研究结果表明, ramucirumab在中国晚期实体瘤患者中耐受性良好, 且不良事件易于管理。
• 中国患者的药代动力学特征与其他人群相似。未检测到免疫原性。
• 无法就疗效得出结论, 需要开展进一步的随机研究。
摘要
背景. 本研究是一项单臂、非随机、开放性、剂量递增、I期研究, 在对标准治疗耐药或无可用标准治疗的中国晚期实体瘤患者中评价了ramucirumab的安全性、耐受性和药代动力学（PK）。
方法. 采用3 + 3剂量递增设计, 并在队列2和3中进行扩展PK评价。Ramucirumab以3种不同剂量静脉注射给药：6 mg/kg每2周一次、10 mg/kg每3周一次和8 mg/kg每2周一次。对所有患者进行安全性分析。还评估了PK、免疫原性和抗肿瘤活性。
结果. 28例治疗患者中有2例出现了剂量限制性毒性, 可能与ramucirumab相关。未确定最大耐受剂量。所有患者均出现了至少1例治疗开始后不良事件。53.6%（n=15）的患者报告了≥3级不良事件。PK分析显示, 与其他人群一致, ramucirumab在中国患者体内的清除率低、分布容积小且半衰期长。未检测到免疫原性。患者均未达到完全/部分缓解, 64.3%（n=18）达到疾病稳定, 中位持续时间为5.55个月（95%置信区间：3.38‐7.13个月）。
结论. Ramucirumab在中国晚期实体瘤患者中耐受性良好。中国患者的PK特征与其他人群相似。The Oncologist 2017;22:638–e56
Trial registration: ClinicalTrials.gov NCT01682135.
© AlphaMed Press; the data published online to support this summary is the property of the authors.