Saitama Cancer Center, Saitama, Japan.
Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Gastric Cancer. 2018 Nov;21(6):1041-1049. doi: 10.1007/s10120-018-0811-4. Epub 2018 Mar 5.
Ramucirumab, a monoclonal antibody vascular endothelial growth factor receptor-2 antagonist, given as monotherapy improved survival in a global phase 3 study (REGARD) of patients with gastric cancer. However, REGARD did not include Japanese patients. This study evaluated the efficacy and safety of ramucirumab monotherapy in Japanese patients with advanced gastric cancer.
This multicenter, open-label, nonrandomized phase 2 study (Clinicaltrials.gov: NCT01983878) was performed at 16 Japanese sites. Patients with advanced gastric or gastroesophageal junction cancer after disease progression following first-line chemotherapy received intravenous ramucirumab 8 mg/kg every 2 weeks. Primary efficacy outcome: 12-week progression-free survival rate (PFS).
Thirty-six patients were enrolled. The 12-week PFS rate was 23.8% [90% confidence interval (CI) 12.4-37.2); the primary outcome was not met as the lower limit of the CI was outside the threshold of 16%. Median PFS was 6.6 weeks (90% CI 6.1-7.1). No patients achieved an objective response, and 11 (31%) patients achieved disease control. Median overall survival was 8.6 months (90% CI 5.7-10.7). The most frequent treatment-emergent adverse events (TEAEs) were diarrhea (9/36; 25%) and decreased appetite (8/36; 22%). Three patients reported Grade ≥ 3 ileus; all other Grade ≥ 3 TEAEs were reported by ≤ 2 patients. The most frequent adverse events of special interest (AESIs) were hypertension (10/36; 28%), bleeding/hemorrhage (7/36; 19%), and proteinuria (7/36; 19%). All Grade ≥ 3 AESIs were reported by ≤ 2 patients.
These findings suggest that ramucirumab monotherapy has clinical activity and a manageable safety profile in Japanese patients with gastric cancer after disease progression following first-line chemotherapy.
雷莫芦单抗是一种单克隆抗体血管内皮生长因子受体-2 拮抗剂，在全球 3 期研究（REGARD）中作为单药治疗，改善了胃癌患者的生存。然而，REGARD 不包括日本患者。本研究评估了雷莫芦单抗单药治疗日本晚期胃癌患者的疗效和安全性。
这是一项多中心、开放性、非随机 2 期研究（Clinicaltrials.gov：NCT01983878），在 16 个日本地点进行。在一线化疗后疾病进展的晚期胃癌或胃食管交界处癌患者接受静脉注射雷莫芦单抗 8mg/kg，每 2 周一次。主要疗效终点：12 周无进展生存率（PFS）。
共纳入 36 例患者。12 周 PFS 率为 23.8%[90%置信区间（CI）12.4-37.2]；下限低于 16%，未达到预设的 12 周 PFS 率目标。中位 PFS 为 6.6 周（90%CI 6.1-7.1）。无患者获得客观缓解，11 例（31%）患者获得疾病控制。中位总生存期为 8.6 个月（90%CI 5.7-10.7）。最常见的治疗相关不良事件（TEAEs）为腹泻（36 例中有 9 例；25%）和食欲下降（36 例中有 8 例；22%）。有 3 例患者报告出现 Grade≥3 肠梗阻；所有其他 Grade≥3 TEAEs 均报告发生于≤2 例患者。最常见的治疗相关不良事件（AESI）为高血压（36 例中有 10 例；28%）、出血/出血（36 例中有 7 例；19%）和蛋白尿（36 例中有 7 例；19%）。所有 Grade≥3 AESI 均报告发生于≤2 例患者。
这些结果表明，雷莫芦单抗单药治疗在一线化疗后疾病进展的日本胃癌患者中具有临床活性和可管理的安全性。
