Exploratory Biomarker Analysis Using Plasma Angiogenesis-Related Factors and Cell-Free DNA in the TRUSTY Study: A Randomized, Phase II/III Study of Trifluridine/Tipiracil Plus Bevacizumab as Second-Line Treatment for Metastatic Colorectal Cancer.

IF 4.4 3区医学 Q2 ONCOLOGY

Targeted Oncology Pub Date : 2024-01-01 Epub Date: 2024-01-09 DOI:10.1007/s11523-023-01027-8

Yu Sunakawa, Yasutoshi Kuboki, Jun Watanabe, Tetsuji Terazawa, Hisato Kawakami, Mitsuru Yokota, Masato Nakamura, Masahito Kotaka, Naotoshi Sugimoto, Hitoshi Ojima, Eiji Oki, Takeshi Kajiwara, Yoshiyuki Yamamoto, Yasushi Tsuji, Tadamichi Denda, Takao Tamura, Soichiro Ishihara, Hiroya Taniguchi, Takako Eguchi Nakajima, Satoshi Morita, Kuniaki Shirao, Naruhito Takenaka, Daisuke Ozawa, Takayuki Yoshino

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引用次数: 0

Abstract

Background: The TRUSTY study evaluated the efficacy of second-line trifluridine/tipiracil (FTD/TPI) plus bevacizumab in metastatic colorectal cancer (mCRC).

Objective: This exploratory biomarker analysis of TRUSTY investigated the relationship between baseline plasma concentrations of angiogenesis-related factors and cell-free DNA (cfDNA), and the efficacy of FTD/TPI plus bevacizumab in patients with mCRC.

Patients and methods: The disease control rate (DCR) and progression-free survival (PFS) were compared between baseline plasma samples of patients with high and low plasma concentrations (based on the median value) of angiogenesis-related factors. Correlations between cfDNA concentrations and PFS were assessed.

Results: Baseline characteristics (n = 65) were as follows: male/female, 35/30; median age, 64 (range 25-84) years; and RAS status wild-type/mutant, 29/36. Patients in the hepatocyte growth factor (HGF)-low and interleukin (IL)-8-low groups had a significantly higher DCR (risk ratio [95% confidence intervals {CIs}]) than patients in the HGF-high (1.83 [1.12-2.98]) and IL-8-high (1.70 [1.02-2.82]) groups. PFS (hazard ratio {HR} [95% CI]) was significantly longer in patients in the HGF-low (0.33 [0.14-0.79]), IL-8-low (0.31 [0.14-0.70]), IL-6-low (0.19 [0.07-0.50]), osteopontin-low (0.39 [0.17-0.88]), thrombospondin-2-low (0.42 [0.18-0.98]), and tissue inhibitor of metalloproteinase-1-low (0.26 [0.10-0.67]) groups versus those having corresponding high plasma concentrations of these angiogenesis-related factors. No correlation was observed between cfDNA concentration and PFS.

Conclusion: Low baseline plasma concentrations of HGF and IL-8 may predict better DCR and PFS in patients with mCRC receiving FTD/TPI plus bevacizumab, however further studies are warranted.

Clinical trial registration number: jRCTs031180122.

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在 TRUSTY 研究中使用血浆血管生成相关因子和游离细胞 DNA 进行探索性生物标志物分析：曲氟尿苷/替拉西嘧啶加贝伐单抗作为转移性结直肠癌二线治疗的随机 II/III 期研究》。

研究背景TRUSTY研究评估了转移性结直肠癌（mCRC）二线三氟啶/替吡拉西（FTD/TPI）加贝伐珠单抗的疗效：这项TRUSTY探索性生物标志物分析研究了血管生成相关因子和无细胞DNA（cfDNA）的基线血浆浓度与FTD/TPI加贝伐单抗治疗mCRC患者疗效之间的关系：比较了血管生成相关因子浓度较高和较低（基于中位值）的患者基线血浆样本的疾病控制率（DCR）和无进展生存期（PFS）。评估了 cfDNA 浓度与 PFS 之间的相关性：基线特征（n = 65）如下：男性/女性，35/30；中位年龄，64（范围 25-84）岁；RAS 状态野生型/突变型，29/36。肝细胞生长因子（HGF）低组和白细胞介素（IL）-8低组患者的DCR（风险比[95%置信区间{CIs}]）显著高于HGF高组（1.83 [1.12-2.98] ）和IL-8高组（1.70 [1.02-2.82]）。HGF-低（0.33 [0.14-0.79] ）、IL-8-低（0.31 [0.14-0.70] ）、IL-6-低（0.19 [0.07-0.50] ）、Osteopontin-低（0.39 [0.17-0.88]）、凝血酶原-2-低（0.42 [0.18-0.98] ）和组织金属蛋白酶抑制剂-1-低（0.26 [0.10-0.67] ）组与这些血管生成相关因子血浆浓度相应较高的组相比。cfDNA浓度与PFS之间没有相关性：临床试验注册号：jRCTs031180122。

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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.