Cancer Treatment Center, Kansai Medical University Hospital, 2-3-1, Shinmachi, Hirakata-shi, Osaka, 5731191, Japan.
Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaragi, Japan.
Target Oncol. 2024 Mar;19(2):181-190. doi: 10.1007/s11523-024-01043-2. Epub 2024 Mar 1.
Non-inferiority of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) to irinotecan/fluoropyrimidine plus BEV in metastatic colorectal cancer was investigated in the phase III TRUSTY study, and we conducted a phase II study of FOLFIRI (5-FU+leucovorin+irinotecan) plus zib-aflibercept (AFL) after FTD/TPI plus BEV. However, the TRUSTY study failed during the recruitment of our patients.
We present the findings of a phase II study on the efficacy of FOLFIRI plus zib-aflibercept (AFL) after FTD/TPI plus BEV, including clinical results with plasma biomarker analyses.
This was a multicenter, single-arm, phase II study in patients with metastatic colorectal cancer refractory or intolerant to oxaliplatin, fluoropyrimidine, BEV, and FTD/TPI. The primary endpoint was progression-free survival. Fifteen plasma angiogenesis-associated biomarkers were analyzed using a Luminex multiplex assay U-kit.
Between January 2020 and May 2022, 26 patients (median age, 68 years) from 15 sites were enrolled. The median progression-free survival was 4.9 months (85% confidence interval, 3.4 month-not estimated). The overall response and disease control rates were 8% and 62%, respectively. The median levels of vascular endothelial growth factor-A and placental growth factor, both targets of AFL, were below the measurable limit of 30 pg/mL and 16 pg/mL, respectively. Patients were divided into two groups at the median levels of baseline biomarkers. The progression-free survival did not differ between high and low expressers of placental growth factor (p = 0.7), while it tended to be shorter in those with high levels of osteopontin (p = 0.05), angiopoietin-2 (p = 0.07), and tissue inhibitor of matrix metalloproteinases-1 (p = 0.1).
This study did not meet the primary endpoint. Hence, FOLFIRI plus AFL should not be used after FTD/TPI plus BEV for metastatic colorectal cancer. Further studies are needed to determine factors not targeted by AFL that may affect the efficacy of the treatment.
jRCTs041190100.
在 III 期 TRUSTY 研究中，研究了替匹嘧啶/曲氟尿苷（FTD/TPI）联合贝伐珠单抗（BEV）与伊立替康/氟嘧啶联合 BEV 相比在转移性结直肠癌中的非劣效性，并且我们在 FTD/TPI 联合 BEV 后进行了 FOLFIRI（5-FU+亚叶酸+伊立替康）联合 Zib-aflibercept（AFL）的 II 期研究。然而，TRUSTY 研究在招募我们的患者时失败了。
我们介绍了 FTD/TPI 联合 BEV 后 FOLFIRI 联合 Zib-aflibercept（AFL）的疗效的 II 期研究结果，包括基于血浆生物标志物分析的临床结果。
这是一项在转移性结直肠癌患者中进行的多中心、单臂、II 期研究，这些患者对奥沙利铂、氟嘧啶、BEV 和 FTD/TPI 耐药或不耐受。主要终点是无进展生存期。使用 Luminex 多重分析试剂盒 U-kit 分析了 15 种与血管生成相关的血浆生物标志物。
2020 年 1 月至 2022 年 5 月，来自 15 个地点的 26 名（中位年龄 68 岁）患者入组。中位无进展生存期为 4.9 个月（85%置信区间：3.4 个月-未估计）。总缓解率和疾病控制率分别为 8%和 62%。AFL 的两个靶点血管内皮生长因子-A 和胎盘生长因子的中位水平均低于 30pg/mL 和 16pg/mL 的可测量下限。根据基线生物标志物的中位数水平将患者分为两组。胎盘生长因子高表达组和低表达组的无进展生存期无差异（p=0.7），而高表达骨桥蛋白（p=0.05）、血管生成素-2（p=0.07）和基质金属蛋白酶组织抑制剂-1（p=0.1）的患者无进展生存期倾向较短。
本研究未达到主要终点。因此，对于转移性结直肠癌，FTD/TPI 联合 BEV 后不应使用 FOLFIRI 联合 AFL。需要进一步研究确定 AFL 未靶向的可能影响治疗效果的因素。
jRCTs041190100。
