曲妥珠单抗联合 S-1 和奥沙利铂治疗化疗初治的 HER2 阳性晚期胃癌的多中心 II 期研究。
Multicenter phase II study of trastuzumab with S-1 plus oxaliplatin for chemotherapy-naïve, HER2-positive advanced gastric cancer.
机构信息
Department of Gastroenterology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Department of Clinical Trial Planning and Management, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
出版信息
Gastric Cancer. 2019 Nov;22(6):1238-1246. doi: 10.1007/s10120-019-00973-5. Epub 2019 May 17.
BACKGROUND
Trastuzumab with cisplatin and fluoropyrimidines improves overall survival (OS) in patients with HER2-positive advanced gastric cancer (AGC). S-1 plus oxaliplatin (SOX) is one of the standard regimens for HER2-negative AGC in Japan. However, few studies have evaluated trastuzumab combined with SOX in patients with HER2-positive AGC.
METHODS
This was a multicenter, phase II study conducted at 10 institutions in Japan. Patients with HER2-positive AGC received S-1 twice a day on days 1-14 and oxaliplatin and trastuzumab on day 1 of a 21-day cycle. The primary endpoint was the confirmed overall response rate (ORR), and the secondary endpoints were OS, progression-free survival (PFS), and safety. The sample size was 75 to have 90% power with an alpha error of 0.1 (one-sided), expecting an ORR of 65% and threshold of 50%.
RESULTS
From June 2015 to January 2018, 75 patients were enrolled. The ORR was 70.7% [95% confidence interval (CI) 59.0-80.6]. The median OS and PFS were estimated as 18.1 months (95% CI 15.6-26.5) and 8.8 months (95% CI 7.4-12.2), respectively. The major grade 3 or 4 adverse events were sensory neuropathy (16.0%) and neutropenia (10.7%).
CONCLUSIONS
Trastuzumab with SOX had promising activity with well-tolerated toxicities for patients with HER2-positive AGC.
CLINICAL TRIAL REGISTRATION
UMIN000017602.
背景
曲妥珠单抗联合顺铂和氟嘧啶可改善人表皮生长因子受体 2（HER2）阳性晚期胃癌（AGC）患者的总生存期（OS）。S-1 联合奥沙利铂（SOX）是日本 HER2 阴性 AGC 的标准方案之一。然而，很少有研究评估曲妥珠单抗联合 SOX 治疗 HER2 阳性 AGC 患者。
方法
这是一项在日本 10 家机构进行的多中心、Ⅱ期研究。HER2 阳性 AGC 患者接受 S-1 每日两次，第 1-14 天，第 1 天接受奥沙利铂和曲妥珠单抗，每 21 天为一个周期。主要终点为确认的总缓解率（ORR），次要终点为 OS、无进展生存期（PFS）和安全性。样本量为 75 例，以 90%的效能和 0.1（单侧）的α误差，预计 ORR 为 65%，阈值为 50%。
结果
从 2015 年 6 月至 2018 年 1 月，共纳入 75 例患者。ORR 为 70.7%[95%可信区间（CI）59.0-80.6]。中位 OS 和 PFS 分别估计为 18.1 个月（95%CI 15.6-26.5）和 8.8 个月（95%CI 7.4-12.2）。主要的 3 级或 4 级不良事件为感觉神经病变（16.0%）和中性粒细胞减少症（10.7%）。
结论
曲妥珠单抗联合 SOX 对 HER2 阳性 AGC 患者具有良好的疗效和可耐受的毒性。
临床试验注册
UMIN000017602。
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