Baeksgaard Jensen Lene, Yilmaz Mette, Nordsmark Marianne, Möller Sören, Elle Ida Coordt, Ladekarl Morten, Qvortrup Camilla, Pfeiffer Per
Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
Department of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
EClinicalMedicine. 2024 Mar 8;70:102521. doi: 10.1016/j.eclinm.2024.102521. eCollection 2024 Apr.
Trifluridine-tipiracil has shown a survival benefit compared with placebo in patients with chemorefractory metastatic esophago-gastric adenocarcinoma. We aimed to compare the efficacy of trifluridine-tipiracil plus bevacizumab vs trifluridine-tipiracil monotherapy in pre-treated patients with metastatic esophago-gastric adenocarcinoma.
This investigator-initiated, open-label, randomized trial enrolled patients with metastatic esophago-gastric adenocarcinoma. The main inclusion criteria were patients with pre-treated metastatic esophago-gastric adenocarcinoma, and WHO performance status 0 or 1. Participants were randomly assigned (1:1) to receive oral trifluridine-tipiracil (35 mg/m twice daily on days 1-5 and 8-12 every 28 days) alone or combined with bevacizumab (5 mg/kg on days 1 and 15) until progression, unacceptable toxicity, or patient decision to withdraw. Randomisation was stratified by sex and treatment line. The primary endpoint was investigator-evaluated progression-free survival. All analyses were based on intention to treat. This trial is registered with EudraCT, 2018-004845-18.
From Oct 1, 2019, to Sept 30, 2021, 103 patients were enrolled and randomly assigned to trifluridine-tipiracil (n = 53) or trifluridine-tipiracil plus bevacizumab (n = 50). The clinical cut-off date was March 1st, 2023, after a median follow-up of 36.6 months. Median progression-free survival was 3.1 months (95% CI 2.0-4.3) in the trifluridine-tipiracil group vs 3.9 months (3.0-6.3) in the trifluridine-tipiracil plus bevacizumab group (hazard ratio 0.68, 95% CI 0.46-1.02; p = 0.058). The most frequent grade 3 or worse adverse event was neutropenia, observed in 26 (49%) patients in the trifluridine-tipiracil group vs 23 patients (46%) in the trifluridine-tipiracil plus bevacizumab group. At least one hospitalization was observed in 21 patients (40%) in the trifluridine-tipiracil group and 22 patients (44%) in the trifluridine-tipiracil plus bevacizumab group. No deaths were deemed treatment related.
In patients with pre-treated metastatic esophago-gastric cancer, trifluridine-tipiracil plus bevacizumab, compared to trifluridine-tipiracil monotherapy, did not significantly prolong progression-free survival. The combination of trifluridine-tipiracil with bevacizumab was well tolerated without increase in severe neutropenia and no new safety signals.
Servier, Roche.
与安慰剂相比，曲氟尿苷-替匹嘧啶已显示出对化疗难治性转移性食管胃腺癌患者具有生存获益。我们旨在比较曲氟尿苷-替匹嘧啶联合贝伐珠单抗与曲氟尿苷-替匹嘧啶单药治疗在转移性食管胃腺癌预处理患者中的疗效。
这项由研究者发起的开放标签随机试验纳入了转移性食管胃腺癌患者。主要纳入标准为转移性食管胃腺癌预处理患者，且世界卫生组织体能状态为0或1。参与者被随机分配（1:1）接受口服曲氟尿苷-替匹嘧啶（每28天的第1 - 5天和第8 - 12天每天两次，每次35 mg/m²）单独治疗或联合贝伐珠单抗（第1天和第15天5 mg/kg），直至疾病进展、出现不可接受的毒性或患者决定退出。随机分组按性别和治疗线进行分层。主要终点是研究者评估的无进展生存期。所有分析均基于意向性治疗。该试验已在欧洲临床试验数据库（EudraCT）注册，注册号为2018 - 004845 - 18。
从2019年10月1日至2021年9月30日，103例患者入组并随机分配至曲氟尿苷-替匹嘧啶组（n = 53）或曲氟尿苷-替匹嘧啶联合贝伐珠单抗组（n = 50）。临床截止日期为2023年3月1日，中位随访时间为36.6个月。曲氟尿苷-替匹嘧啶组的中位无进展生存期为3.1个月（95%CI 2.0 - 4.3），而曲氟尿苷-替匹嘧啶联合贝伐珠单抗组为3.9个月（3.0 - 6.3）（风险比0.68，95%CI 0.46 - 1.02；p = 0.058）。最常见的3级或更严重不良事件是中性粒细胞减少，曲氟尿苷-替匹嘧啶组有26例（49%）患者出现，曲氟尿苷-替匹嘧啶联合贝伐珠单抗组有23例（46%）患者出现。曲氟尿苷-替匹嘧啶组有21例（40%）患者至少住院一次，曲氟尿苷-替匹嘧啶联合贝伐珠单抗组有22例（44%）患者至少住院一次。未发现与治疗相关的死亡病例。
在转移性食管胃癌预处理患者中，与曲氟尿苷-替匹嘧啶单药治疗相比，曲氟尿苷-替匹嘧啶联合贝伐珠单抗并未显著延长无进展生存期。曲氟尿苷-替匹嘧啶与贝伐珠单抗联合耐受性良好，未增加严重中性粒细胞减少的发生率，也未出现新的安全信号。
施维雅公司、罗氏公司。
Zotero 插件
