随机 II 期试验：替氟尿苷/盐酸替匹嘧啶（FTD/TPI）联合雷莫芦单抗（RAM）对比替氟尿苷/盐酸替匹嘧啶治疗既往治疗的晚期胃或胃食管结合部腺癌患者（RETRIEVE 研究，WJOG15822G）。
Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G).
机构信息
Department of Gastroenterology, Saitama Cancer Center, 780 Komuro, Ina-Machi, Kita-Adachi-Gun, Saitama, 362-0807, Japan.
Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, 35 Shinanomachi, Tokyo, 160-8582, Japan.
出版信息
BMC Cancer. 2023 Aug 5;23(1):726. doi: 10.1186/s12885-023-11199-1.
BACKGROUND
Trifluridine/tipiracil (FTD/TPI) prolongs survival in the third- or later-line treatment for advanced gastric cancer (GC), esophagogastric junction (EGJ) adenocarcinoma, and colorectal cancer. While single-arm phase II trials showed promising outcomes of FTD/TPI plus ramucirumab (RAM) as third- or later-line treatments for advanced GC or EGJ cancer, there have been no clinical trials to directly compare FTD/TPI plus RAM with FTD/TPI monotherapy. Therefore, we have started a randomised phase II trial to evaluate the efficacy and safety of FTD/TPI plus RAM compared with FTD/TPI monotherapy as third- or later-line treatments in patients with advanced GC and EGJ adenocarcinoma.
METHODS
This RETREVE trial (WJOG15822G) is a prospective, open-label, randomised, multicentre phase II trial comparing FTD/TPI plus RAM versus FTD/TPI monotherapy in a third- or later-line setting. Eligibility criteria include age of > 20 years; performance status of 0 or 1; unresectable or recurrent gastric or EGJ adenocarcinoma; confirmed HER2 status; refractory or intolerant to fluoropyrimidine, taxane or irinotecan; refractory to RAM (not intolerant); and at least a measurable lesion per RECIST 1.1. FTD/TPI (35 mg/m twice daily, evening of day 1 to morning of day 6 and evening of day 8 to morning of day 13) was administered orally every 4 weeks, and RAM (8 mg/kg) was administered intravenously every 2 weeks. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival, objective response rate, disease control rate, and safety. The expected hazard ratio of PFS is set as 0.7, assuming 4-month PFS rate of 27% in FTD/TPI monotherapy and 40% in FTD/TPI plus RAM. The number of subjects was 110, with a one-sided alpha error of 0.10 and power of 0.70.
DISCUSSION
This study will clarify the additional effect of RAM continuation beyond disease progression on FTD/TPI in the third- or later-line setting for patients with advanced GC or EGJ cancer.
TRIAL REGISTRATION
jRCTs041220120.
背景
曲氟尿苷替匹嘧啶（FTD/TPI）可延长三线或后线晚期胃癌（GC）、食管胃结合部（EGJ）腺癌和结直肠癌的生存时间。虽然单臂 II 期试验表明 FTD/TPI 联合雷莫芦单抗（RAM）作为晚期 GC 或 EGJ 癌症的三线或后线治疗具有良好的疗效，但尚无临床试验直接比较 FTD/TPI 联合 RAM 与 FTD/TPI 单药治疗。因此，我们开展了一项随机 II 期试验，以评估 FTD/TPI 联合 RAM 与 FTD/TPI 单药作为晚期 GC 和 EGJ 腺癌三线或后线治疗的疗效和安全性。
方法
这项 RETREVE 试验（WJOG15822G）是一项前瞻性、开放标签、随机、多中心 II 期试验，比较了 FTD/TPI 联合 RAM 与 FTD/TPI 单药在三线或后线治疗中的疗效。入选标准包括年龄>20 岁；体力状态 0 或 1 级；不可切除或复发性胃或 EGJ 腺癌；HER2 状态明确；氟嘧啶、紫杉烷或伊立替康耐药或不耐受；对 RAM 耐药（不耐受）；且根据 RECIST 1.1 标准至少有一个可测量病灶。FTD/TPI（35mg/m，每日两次，第 1 天晚上至第 6 天早上，第 8 天晚上至第 13 天早上）每 4 周口服，RAM（8mg/kg）每 2 周静脉注射。主要终点是无进展生存期（PFS），次要终点是总生存期、客观缓解率、疾病控制率和安全性。假设 FTD/TPI 单药治疗的 4 个月 PFS 率为 27%，FTD/TPI 联合 RAM 治疗的 4 个月 PFS 率为 40%，则 PFS 的预期风险比设定为 0.7。需要入组 110 例患者，单侧 α 错误为 0.10，功效为 0.70。
讨论
本研究将明确在晚期 GC 或 EGJ 癌症三线或后线治疗中，在疾病进展后继续使用 RAM 对 FTD/TPI 的附加疗效。
试验注册
jRCTs041220120。
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