Authors' Affiliations: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; David Geffen School of Medicine, University of California, Los Angeles, California; Northwestern University Feinberg School of Medicine, Chicago Illinois; East Jefferson General Hospital, Metairie, Louisiana; Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; ImClone Systems, a wholly-owned subsidiary of Eli Lilly and company, Bridgewater, New Jersey; Eli Lilly and Company, Indianapolis, Indiana; and Lahey Hospital and Medical Center, Tufts University School of Medicine, Burlington, Massachusetts.
Clin Cancer Res. 2013 Dec 1;19(23):6614-23. doi: 10.1158/1078-0432.CCR-13-1442. Epub 2013 Oct 2.
To assess the efficacy and safety of the anti-VEGF receptor-2 (VEGFR-2) antibody ramucirumab as first-line therapy in patients with advanced hepatocellular carcinoma and explore potential circulating biomarkers.
Adults with advanced hepatocellular carcinoma and no prior systemic treatment received ramucirumab 8 mg/kg every two weeks until disease progression or limiting toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR) and overall survival (OS). Circulating biomarkers were evaluated before and after ramucirumab treatment in a subset of patients.
Forty-two patients received ramucirumab. Median PFS was 4.0 months [95% confidence interval (CI), 2.6-5.7], ORR was 9.5% (95% CI, 2.7-22.6; 4/42 patients had a partial response), and median OS was 12.0 months (95% CI, 6.1-19.7). For patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease, median OS was 4.4 months (95% CI, 0.5-9.0) for patients with Child-Pugh B cirrhosis versus 18.0 months (95% CI, 6.1-23.5) for patients with Child-Pugh A cirrhosis. Treatment-related grade ≥ 3 toxicities included hypertension (14%), gastrointestinal hemorrhage and infusion-related reactions (7% each), and fatigue (5%). There was one treatment-related death (gastrointestinal hemorrhage). After treatment with ramucirumab, there was an increase in serum VEGF and placental growth factor (PlGF) and a transient decrease in soluble VEGFR-2.
Ramucirumab monotherapy may confer anticancer activity in advanced hepatocellular carcinoma with an acceptable safety profile. Exploratory biomarker studies showed changes in circulating VEGF, PlGF, and sVEGFR-2 that are consistent with those seen with other anti-VEGF agents.
评估抗血管内皮生长因子受体-2（VEGFR-2）抗体雷莫芦单抗作为晚期肝细胞癌一线治疗的疗效和安全性，并探索潜在的循环生物标志物。
未接受过系统治疗的晚期肝细胞癌成人患者接受雷莫芦单抗 8mg/kg，每两周一次，直至疾病进展或出现限制毒性。主要终点是无进展生存期（PFS）；次要终点包括客观缓解率（ORR）和总生存期（OS）。在一部分患者中，在接受雷莫芦单抗治疗前后评估了循环生物标志物。
42 名患者接受了雷莫芦单抗治疗。中位 PFS 为 4.0 个月[95%置信区间（CI），2.6-5.7]，ORR 为 9.5%（95%CI，2.7-22.6；4/42 例患者有部分缓解），中位 OS 为 12.0 个月（95%CI，6.1-19.7）。对于巴塞罗那临床肝癌（BCLC）分期 C 期疾病患者，Child-Pugh B 级肝硬化患者的中位 OS 为 4.4 个月（95%CI，0.5-9.0），而 Child-Pugh A 级肝硬化患者的中位 OS 为 18.0 个月（95%CI，6.1-23.5）。与治疗相关的≥3 级毒性包括高血压（14%）、胃肠道出血和输注相关反应（各 7%）以及疲劳（5%）。有 1 例与治疗相关的死亡（胃肠道出血）。接受雷莫芦单抗治疗后，血清 VEGF 和胎盘生长因子（PlGF）增加，可溶性 VEGFR-2 短暂下降。
雷莫芦单抗单药治疗可能对晚期肝细胞癌具有抗肿瘤活性，安全性可接受。探索性生物标志物研究显示，循环 VEGF、PlGF 和 sVEGFR-2 的变化与其他抗 VEGF 药物一致。
