Department of Neurology and the Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
J Neurooncol. 2012 Apr;107(2):407-11. doi: 10.1007/s11060-011-0768-1. Epub 2011 Dec 28.
Glioblastoma (GBM) is a highly vascular tumor dependent on angiogenesis through the vascular endothelial growth factor (VEGF) signaling cascade. Inhibition of VEGF signaling is an important therapeutic strategy. We report our experience with bevacizumab (BEV), a VEGF targeting antibody, following failure of a VEGF receptor targeting tyrosine kinase inhibitor (TKI). We retrospectively identified patients treated on clinical trials with VEGFR-TKIs for recurrent GBM followed by BEV at next recurrence. Survival was estimated by the Kaplan-Meier method. Fourteen patients were identified (six women; median age 57). All received VEGFR-TKIs (sunitinib 11, cediranib 2, sorafenib 1) then BEV at next recurrence. There were no radiographic responses to VEGFR-TKIs; best response was stable disease in 50% (7/14). Patients received BEV alone (21%, 3/14) or in combination with chemotherapy (79%, 11/14). On BEV, 29% (4/14) had a partial response, and 36% (5/14) stabilized. Of evaluable patients, 42% (5/12) had neurological improvement and 56% (5/9) reduced corticosteroid requirement. Median survival on BEV was 7.8 months (95% CI 4.0-15.8), median progression-free survival (PFS) was 4.0 months (95% CI 1.6-10.5), and the 6-month PFS rate was 29% (95% CI 9-52). Our radiographic and survival outcomes with BEV following progression after VEGFR-TKIs are similar to data from studies of BEV as initial salvage therapy, although our sample size was small. Prior exposure to VEGFR-TKIs may not preclude response to BEV, but sensitivity to BEV may be lower following more robust VEGFR inhibition.
胶质母细胞瘤（GBM）是一种高度血管依赖性肿瘤，依赖于血管内皮生长因子（VEGF）信号级联通过血管生成。抑制 VEGF 信号是一种重要的治疗策略。我们报告了贝伐单抗（BEV）的经验，贝伐单抗是一种针对 VEGF 的抗体，在 VEGF 受体靶向酪氨酸激酶抑制剂（TKI）治疗失败后使用。我们回顾性地确定了在临床试验中接受 VEGFR-TKIs 治疗复发性 GBM 然后在下一次复发时接受 BEV 治疗的患者。通过 Kaplan-Meier 方法估计生存。确定了 14 名患者（6 名女性；中位年龄 57 岁）。所有人均接受过 VEGFR-TKIs（舒尼替尼 11 例，西地尼布 2 例，索拉非尼 1 例），然后在下一次复发时接受 BEV 治疗。VEGFR-TKIs 无放射学反应；最佳反应为 50%（7/14）的稳定疾病。患者单独接受 BEV（21%，14/14）或与化疗联合（79%，11/14）。在 BEV 上，29%（4/14）有部分反应，36%（5/14）稳定。可评估患者中，42%（5/12）有神经改善，56%（5/9）减少皮质类固醇需求。BEV 的中位生存时间为 7.8 个月（95%CI 4.0-15.8），中位无进展生存期（PFS）为 4.0 个月（95%CI 1.6-10.5），6 个月 PFS 率为 29%（95%CI 9-52）。我们在 VEGFR-TKIs 进展后使用 BEV 的放射学和生存结果与 BEV 作为初始挽救治疗的研究数据相似，尽管我们的样本量较小。先前暴露于 VEGFR-TKIs 可能不会排除对 BEV 的反应，但在更强烈的 VEGFR 抑制后，对 BEV 的敏感性可能会降低。
