Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
Eur J Cancer. 2023 Mar;182:43-52. doi: 10.1016/j.ejca.2022.12.031. Epub 2023 Jan 11.
Although anti-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (RTKIs) have been tested in patients with neuroendocrine tumours (NETs) over the last two decades, no study to date has benchmarked efficacy and toxicity of these drugs in this patient population.
All phase II and phase III studies of anti-VEGF RTKIs in patients with NETs, published between January 1, 2000 andJuly 31, 2021, across major trial databases, were searched in August 2021 for relevant studies. The primary objectives of the meta-analysis were to compare objective response rate (ORR) and progression-free survival (PFS) between patients with pancreatic NETs (pNETs) and extra-pancreatic NETs (epNETs), and the incidence rate ratio (IRR) of adverse events between patients receiving anti-VEGF RTKIs and control.
1611 patients were available for the meta-analysis; 1194 received anti-VEGF RTKIs. ORR in pNETs was 18% (95% confidence interval (CI) 13-25%), while ORR in epNETs was 8% (95% CI 5-12%); test for differences between pNETs and epNETs (x12 = 8.38, p < .01). Median PFS in pNETs was 13.9 months (95% CI 11.43-16.38 months), while median PFS in epNETs was 12.71 months (95% CI 9.37-16.05 months); test for differences between pNETs and epNETs (x12 = .35, p = .55). With regards to common grade 3/4 adverse events , patients who received anti-VEGF RTKIs were more likely to experience hypertension (IRR 3.04, 95% CI 1.63-5.65) and proteinuria (IRR 5.79, 95% CI 1.09-30.74) in comparison to those who received control.
Anti-VEGF RTKIs demonstrate anti-tumour effect in both pNETs and epNETs, supporting their development in both populations. These agents also appear to be safe in patients with NETs.
尽管抗血管内皮生长因子（VEGF）受体酪氨酸激酶抑制剂（RTKIs）在过去二十年中已在神经内分泌肿瘤（NETs）患者中进行了测试，但迄今为止尚无研究对这些药物在该患者人群中的疗效和毒性进行基准测试。
2021 年 8 月，在主要试验数据库中搜索了 2000 年 1 月 1 日至 2021 年 7 月 31 日期间发表的所有关于 NETs 患者抗 VEGF RTKI 的 II 期和 III 期研究，以寻找相关研究。荟萃分析的主要目标是比较胰腺神经内分泌瘤（pNETs）和胰腺外神经内分泌瘤（epNETs）患者的客观缓解率（ORR）和无进展生存期（PFS），以及接受抗 VEGF RTKI 治疗的患者与对照组之间不良事件的发生率比（IRR）。
1611 名患者可用于荟萃分析；1194 名患者接受了抗 VEGF RTKI 治疗。pNETs 的 ORR 为 18%（95%置信区间（CI）为 13-25%），而 epNETs 的 ORR 为 8%（95%CI 为 5-12%）；pNETs 和 epNETs 之间的差异检验（x12=8.38，p<0.01）。pNETs 的中位 PFS 为 13.9 个月（95%CI 11.43-16.38 个月），而 epNETs 的中位 PFS 为 12.71 个月（95%CI 9.37-16.05 个月）；pNETs 和 epNETs 之间的差异检验（x12=0.35，p=0.55）。对于常见的 3/4 级不良事件，接受抗 VEGF RTKI 治疗的患者发生高血压（IRR 3.04，95%CI 1.63-5.65）和蛋白尿（IRR 5.79，95%CI 1.09-30.74）的可能性高于接受对照组的患者。
抗 VEGF RTKI 在 pNETs 和 epNETs 中均具有抗肿瘤作用，支持在这两种人群中开发这些药物。这些药物在 NETs 患者中似乎也是安全的。
