Background

The significance of angiogenic factors as predictors of second-line (2L) chemotherapy efficacy when combined with angiogenesis inhibitors for metastatic colorectal cancer (mCRC) remains unestablished.

Patients and Methods

In this multicenter prospective observational study, 17 angiogenic factors were analyzed in plasma samples collected at pretreatment and progression stages using a Luminex® multiplex assay. Patients who received chemotherapy plus bevacizumab (BEV group), FOLFIRI plus ramucirumab (RAM group), or FOLFIRI plus aflibercept (AFL group) as the 2L treatment were included. Interactions between pretreatment and treatment groups for progression-free survival (PFS), overall survival (OS), and response rate (RR) were assessed using the propensity-score weighted Cox proportional hazards model.

Results

From February 2018 to September 2020, 283 patients were analyzed in the 2L cohort. A strong interaction was observed for PFS between BEV and RAM with HGF, sNeuropilin-1, sVEGFR-1, and sVEGFR-3. Interactions for RR between the BEV and RAM groups were observed for sNeuropilin-1 and sVEGFR-1. Contrarily, OS, PlGF, sVEGFR-1, and sVEGFR-3 differentiated the treatment effect between BEV and AFL. Plasma samples were evaluable for dynamic analysis in 203 patients. At progression, VEGF-A levels significantly decreased in the BEV group and increased in the RAM and AFL groups.

Conclusion

The pretreatment plasma sVEGFR-1 and sVEGFR-3 levels could be predictive biomarkers for distinguishing BEV and RAM when combined with chemotherapy in 2L mCRC treatment. Based on the VEGF-A dynamics at progression, selecting RAM or AFL for patients with significantly elevated VEGF-A levels may be a 2L treatment strategy, with BEV considered for the third-line treatment.

Clinical trial number

UMIN000028616

MicroAbstract: We investigated whether plasma angiogenic factors predict the efficacy of antiangiogenic inhibitor combined with chemotherapy in second-line (2L) treatment of metastatic colorectal cancer (mCRC). Plasma angiogenic factor dynamics at progression during 2L was also evaluated. Pretreatment plasma sVEGFR-1 and sVEGFR-3 levels might be predictive biomarkers for distinguishing between bevacizumab and ramucirumab when combined with chemotherapy in the 2L treatment of mCRC.

中文翻译：

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血浆血管生成因子作为二线化疗联合血管生成抑制剂治疗转移性结直肠癌疗效的预测因子：GI-SCREEN CRC-Ukit 研究结果

背景

当与血管生成抑制剂联合治疗转移性结直肠癌 (mCRC) 时，血管生成因子作为二线 (2L) 化疗疗效预测因子的重要性尚未确定。

患者和方法

在这项多中心前瞻性观察研究中，使用 Luminex® 多重检测对预处理和进展阶段收集的血浆样本中的 17 种血管生成因子进行了分析。纳入接受化疗加贝伐单抗（BEV 组）、FOLFIRI 加雷莫芦单抗（RAM 组）或 FOLFIRI 加阿柏西普（AFL 组）作为 2L 治疗的患者。使用倾向评分加权 Cox 比例风险模型评估预处理组和治疗组之间无进展生存期 (PFS)、总生存期 (OS) 和缓解率 (RR) 的相互作用。

结果

从 2018 年 2 月到 2020 年 9 月，2L 队列中的 283 名患者进行了分析。观察到 BEV 和 RAM 与 HGF、sNeuropilin-1、sVEGFR-1 和 sVEGFR-3 之间的 PFS 存在强烈的相互作用。观察了 BEV 组和 RAM 组之间 sNeuropilin-1 和 sVEGFR-1 的 RR 相互作用。相反，OS、PlGF、sVEGFR-1 和 sVEGFR-3 区分了 BEV 和 AFL 的治疗效果。203 名患者的血浆样本可用于动态分析。进展时，BEV 组的 VEGF-A 水平显着下降，RAM 和 AFL 组的 VEGF-A 水平显着上升。

结论

治疗前血浆 sVEGFR-1 和 sVEGFR-3 水平可以作为 2L mCRC 治疗中与化疗联合使用时区分 BEV 和 RAM 的预测生物标志物。根据进展时的 VEGF-A 动态，为 VEGF-A 水平显着升高的患者选择 RAM 或 AFL 可能是 2L 治疗策略，BEV 考虑作为三线治疗。

临床试验编号

UMIN000028616

MicroAbstract：我们研究了血浆血管生成因子是否可以预测抗血管生成抑制剂联合化疗在转移性结直肠癌 (mCRC) 二线 (2L) 治疗中的疗效。还评估了 2L 期间进展时的血浆血管生成因子动态。治疗前血浆 sVEGFR-1 和 sVEGFR-3 水平可能是在 mCRC 2L 治疗中与化疗联合使用时区分贝伐珠单抗和雷莫芦单抗的预测生物标志物。