转移性肾透明细胞癌（ccRCC）中，血管内皮生长因子受体（VEGFR）和免疫检查点是两个主要的治疗靶点。我们研究了抗血管生成持续曝光对转移性ccRCC免疫治疗临床效果的影响。选取了NIVOREN试验中仅接受过一次抗血管生成治疗后服用尼伐普利的患者。根据第一线疗程的持续时间（<6个月，≥6个月），以及长期第一线疗程（≥18个月）的患者进行了反应率、临床获益、无进展生存期（PFS）和总生存期（OS）的前瞻性分析。基线时收集了8种血浆蛋白和细胞因子的循环水平，并根据第一线抗血管生成持续时间进行比较。在354名患者中，有127名（36%）患者接受了第一线抗血管生成治疗<6个月，227名（64%）患者接受了第一线抗血管生成治疗≥6个月。相对的第一线治疗持续时间与尼伐普利的客观反应（20.5% vs. 23.9%，P = .50）或PFS（HR 0.92；P = .421）无关。<6个月组和≥6个月组的中位OS分别为16.6个月和31.3个月。在经过国际转移性肾细胞癌数据库联盟风险、年龄和转移部位调整之后，第一线治疗持续时间较长的患者OS较长（HR 0.73；P = .017）。第一线VEGFR TKI的持续时间与尼伐普利基线时的8种蛋白质和细胞因子的循环水平无关。尼伐普利在二线疗效与第一线VEGFR TKI持续时间无关。但第一线VEGFR TKI持续时间≥6个月与较长的OS相关。版权所有© 2023. Elsevier Inc.出版

In metastatic renal clear cell carcinoma (ccRCC), vascular endothelial growth factor receptor (VEGFR) and immune checkpoint are 2 main therapeutic targets. We investigated the impact of duration exposure to antiangiogenic on immunotherapy clinical outcomes in metastatic ccRCC.Patients from NIVOREN trial who received nivolumab after only 1 prior antiangiogenic therapy were included. Response rate, clinical benefit, progression free survival (PFS) and overall survival (OS) were prospectively analyzed depending on the duration of the first line (< 6 months, ≥6 months) and exploratory in patients with long first line exposure (≥18 months). The circulating levels of 8 plasma proteins and cytokines at baseline were collected and compared according to first line antiangiogenic duration.Among 354 patients, 127 (36%) and 227 (64%) patients had received first line antiangiogenic for < 6months and ≥ 6months respectively. Respective duration of first line therapy was not associated with objective response to nivolumab (20.5% vs. 23.9%, P = .50), or PFS (HR 0.92; P = .421). Median OS was respectively 16.6 and 31.3 months in the <6 and ≥6 months subgroups respectively. Adjusted on international metastatic renal cell carcinoma database consortium risk, age and metastatic site, OS was longer in patients with longer treatment duration in the first line setting (HR 0.73; P = .017). Duration of first line VEGFR TKI was independent from circulating levels of 8 proteins and cytokines at nivolumab baseline.Nivolumab activity in second line is independent from first-line duration of VEGFR TKI. However, first line VEGFR TKI duration ≥ 6 months is associated with longer OS.Copyright © 2023. Published by Elsevier Inc.