Abstract：
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.
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.
摘要：
背景：在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2个主要治疗靶点。我们研究了在转移性ccRCC中持续暴露于抗血管生成对免疫治疗临床结果的影响。
方法：纳入NIVOREN试验仅在1次抗血管生成治疗后接受纳武单抗治疗的患者。响应率,临床获益,根据一线(<6个月,≥6个月）和长期一线暴露（≥18个月）的患者的探索性。收集基线时8种血浆蛋白和细胞因子的循环水平,并根据一线抗血管生成持续时间进行比较。
结果：在354名患者中，127例（36％）和227例（64％）患者分别接受了<6个月和≥6个月的一线抗血管生成治疗。一线治疗的持续时间与对nivolumab的客观反应无关（20.5%vs.23.9%,P=.50），或PFS（HR0.92；P=.421）。<6个月和≥6个月亚组的中位OS分别为16.6个月和31.3个月。根据国际转移性肾细胞癌数据库联盟风险进行了调整，年龄和转移部位，在一线治疗持续时间较长的患者中，OS更长（HR0.73；P=0.017）。一线VEGFRTKI的持续时间与nivolumab基线时8种蛋白质和细胞因子的循环水平无关。
结论：二线Nivolumab活性独立于VEGFRTKI的一线持续时间。然而,一线VEGFRTKI持续时间≥6个月与较长的OS相关。
方法：纳入NIVOREN试验仅在1次抗血管生成治疗后接受纳武单抗治疗的患者。响应率,临床获益,根据一线(<6个月,≥6个月）和长期一线暴露（≥18个月）的患者的探索性。收集基线时8种血浆蛋白和细胞因子的循环水平,并根据一线抗血管生成持续时间进行比较。
结果：在354名患者中，127例（36％）和227例（64％）患者分别接受了<6个月和≥6个月的一线抗血管生成治疗。一线治疗的持续时间与对nivolumab的客观反应无关（20.5%vs.23.9%,P=.50），或PFS（HR0.92；P=.421）。<6个月和≥6个月亚组的中位OS分别为16.6个月和31.3个月。根据国际转移性肾细胞癌数据库联盟风险进行了调整，年龄和转移部位，在一线治疗持续时间较长的患者中，OS更长（HR0.73；P=0.017）。一线VEGFRTKI的持续时间与nivolumab基线时8种蛋白质和细胞因子的循环水平无关。
结论：二线Nivolumab活性独立于VEGFRTKI的一线持续时间。然而,一线VEGFRTKI持续时间≥6个月与较长的OS相关。
