A Phase II Study of FOLFIRI Plus Ziv-Aflibercept After Trifluridine/Tipiracil Plus Bevacizumab in Patients with Metastatic Colorectal Cancer: WJOG 11018G.

IF 4.4 3区医学 Q2 ONCOLOGY

Targeted Oncology Pub Date : 2024-03-01 DOI:10.1007/s11523-024-01043-2

Toshihiko Matsumoto, Yoshiyuki Yamamoto, Masahito Kotaka, Toshiki Masuishi, Yasushi Tsuji, Hirokazu Shoji, Kenro Hirata, Takao Tsuduki, Akitaka Makiyama, Naoki Izawa, Naoki Takahashi, Masahiro Tsuda, Hisateru Yasui, Takashi Ohta, Yosuke Kito, Satoshi Otsu, Shuichi Hironaka, Kentaro Yamazaki, Narikazu Boku, Ichinosuke Hyodo, Kenichi Yoshimura, Kei Muro

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引用次数: 0

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Clinical trial registration: jRCTs041190100.

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转移性结直肠癌患者在使用曲氟尿苷/替比拉西尔加贝伐单抗后使用 FOLFIRI 加 Ziv-Aflibercept 的 II 期研究：WJOG 11018G。

背景：我们在FTD/TPI+BEV之后开展了FOLFIRI（5-FU+亮紫杉醇+伊立替康）+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：我们介绍了一项关于FOLFIRI联合zib-aflibercept（AFL）在FTD/TPI联合BEV后的疗效的II期研究结果，包括临床结果和血浆生物标志物分析：这是一项多中心、单臂、II期研究，对象是对奥沙利铂、氟嘧啶、BEV和FTD/TPI难治或不耐受的转移性结直肠癌患者。主要终点是无进展生存期。使用Luminex®多重检测U-kit分析了15种血浆血管生成相关生物标志物：2020年1月至2022年5月期间，来自15个研究机构的26名患者（中位年龄68岁）入组。中位无进展生存期为4.9个月（85%置信区间为3.4个月，未估算）。总体反应率和疾病控制率分别为8%和62%。血管内皮生长因子-A和胎盘生长因子（均为AFL的靶标）的中位水平分别低于30 pg/mL和16 pg/mL的可测量限度。根据基线生物标志物的中位水平将患者分为两组。胎盘生长因子高表达者和低表达者的无进展生存期没有差异（p = 0.7），而骨松素（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）高表达者的无进展生存期往往较短：本研究未达到主要终点。因此，在 FTD/TPI 加 BEV 治疗转移性结直肠癌后，不应再使用 FOLFIRI 加 AFL。需要进一步研究以确定 AFL 未靶向的、可能影响疗效的因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.