D'Alessandro Rosalba, Refolo Maria Grazia, Schirizzi Annalisa, De Leonardis Giampiero, Donghia Rossella, Guerra Vito, Giannelli Gianluigi, Lolli Ivan Roberto, Laterza Maria Maddalena, De Vita Ferdinando, Messa Caterina, Lotesoriere Claudio
Laboratory of Experimental Oncology, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Italy.
Data Science Unit, National Institute of Gastroenterology - IRCCS “Saverio de Bellis”, Castellana Grotte, Italy.
Front Oncol. 2022 Apr 6;12:862116. doi: 10.3389/fonc.2022.862116. eCollection 2022.
The combination of paclitaxel and ramucirumab is the second-line therapy of choice in the treatment of advanced gastric cancer. To date, no biomarkers are available in gastric cancer to predict the outcome of antiangiogenic therapy. The present prospective study included 35 patients undergoing second-line therapy with ramucirumab and paclitaxel. Serum samples were systematically collected from the beginning of therapy and at each cycle until disease progression. Multiplex analysis of a panel of angiogenic factors identified markers for which the changes at defined time intervals were significantly different in patients with progression-free survival ≤3 (Rapid Progression Group) compared to those with progression-free survival >3 (Control Disease Group). Comparative analysis revealed significantly different results in the two groups of patients for VEGFC and Angiopoietin-2, both involved in angiogenesis and lymphangiogenesis. VEGFC increased in the progressive-disease group, while it decreased in the control-disease group. This decrease persisted beyond the third cycle, and it was statistically significant compared to the basal level in patients with longer progression-free survival. Angiopoietin-2 decreased significantly after 2 months of therapy. At progression time, there was a significant increase in VEGFC and Angiopoietin-2, suggesting the activation pathways counteracting the blockade of VEGFR2 by ramucirumab. Overall results showed that a greater change in VEGFC and Angiopoietin-2 levels measured at the beginning of the third cycle of therapy corresponded to a lower risk of progression and thus to longer progression-free survival.
紫杉醇与雷莫西尤单抗联合用药是晚期胃癌二线治疗的首选方案。迄今为止，胃癌中尚无生物标志物可用于预测抗血管生成治疗的效果。本前瞻性研究纳入了35例接受雷莫西尤单抗和紫杉醇二线治疗的患者。从治疗开始时及每个周期系统性采集血清样本，直至疾病进展。对一组血管生成因子进行多重分析，确定了在无进展生存期≤3的患者（快速进展组）与无进展生存期>3的患者（疾病控制组）中，在规定时间间隔内变化有显著差异的标志物。对比分析显示，在两组患者中，参与血管生成和淋巴管生成的血管内皮生长因子C（VEGFC）和血管生成素-2的结果有显著差异。VEGFC在疾病进展组中升高，而在疾病控制组中降低。这种降低在第三个周期后持续存在，与无进展生存期较长的患者的基线水平相比具有统计学意义。血管生成素-2在治疗2个月后显著降低。在疾病进展时，VEGFC和血管生成素-2显著升高，提示存在抵消雷莫西尤单抗对VEGFR2阻断作用的激活途径。总体结果表明，在治疗第三个周期开始时测量的VEGFC和血管生成素-2水平变化越大，进展风险越低，无进展生存期越长。
