Wang Yawei, Xing Dan, Zhao Meng, Wang Jie, Yang Yang
Department of Electromyography, Tianjin Hospital, Tianjin, China.
Arthritis Clinic & Research Center, Peking University People's Hospital, Peking University, Beijing, China.
PLoS One. 2016 Mar 23;11(3):e0152170. doi: 10.1371/journal.pone.0152170. eCollection 2016.
Currently, the standard treatment for newly diagnosed glioblastoma multiforme (GBM) is maximal safe surgical resection followed by radiation therapy with concurrent and adjuvant temozolomide. However, disease recurs in almost all patients, and the optimal salvage treatment for recurrent GBM remains unclear. We conducted a systematic review and meta-analysis of published clinical trials to assess the efficacy and toxicities of angiogenesis inhibitors alone as salvage treatment in these patients.
Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). Demographic data, treatment regimens, objective response rate (ORR), median progression-free survival (PFS), median overall survival (OS), 6-months PFS rate, 1-year OS and grade 3/4 toxicities were extracted. We also compared the main outcomes of interest between bevacizumab and other angiogenesis inhibitors. All analyses were performed using Comprehensive Meta Analysis software (Version 2.0).
A total of 842 patients were included for analysis: 343 patients were treated with bevacizumab, 386 with other angiogenesis inhibitors and 81 with thalidomide. The pooled ORR, 6-months PFS, and 1-year OS for recurrent GBM patients receiving angiogenesis inhibitors was 20.1%, 19.5% and 29.3%, respectively. The use of single agent bevacizumab in recurrent GBM significantly improved ORR and 6-months PFS when compared to other angiogenesis inhibitors [relative risk (RR) 2.93, 95% CI 1.38-6.21; p = 0.025; and RR 2.36 95% CI 1.46-3.82; p<0.001, respectively], while no significant difference in 1-year OS was found between the two groups (p = 0.07). when compared to thalidomide, bevacizumab treatment in recurrent GBM significantly improved ORR (RR 6.8, 95%CI: 2.64-17.6, p<0.001), but not for 6-months PFS (p = 0.07) and 1-year OS (p = 0.31). As for grade 3/4 toxicities, the common toxicity was hypertension with pooled incidence of 12.1%, while high-grade thromboembolic events (2.2%), hemorrhage (5.1%) and GI perforation (2.8%) associated with angiogenesis inhibitors were relatively low.
In comparison with other angiogenesis inhibitors and thalidomide, the use of single agent bevacizumab as salvage treatment for recurrent GBM patients improve ORR and 6-months PFS, but not for 1-year OS.
目前，新诊断的多形性胶质母细胞瘤（GBM）的标准治疗方法是最大程度的安全手术切除，随后进行放疗并同步及辅助使用替莫唑胺。然而，几乎所有患者的疾病都会复发，而复发性GBM的最佳挽救治疗方法仍不明确。我们对已发表的临床试验进行了系统评价和荟萃分析，以评估单独使用血管生成抑制剂作为这些患者挽救治疗的疗效和毒性。
通过对公共数据库（MEDLINE、EMBASE、Cochrane图书馆）进行电子检索，确定1994年至2015年间发表的试验。提取人口统计学数据、治疗方案、客观缓解率（ORR）、无进展生存期（PFS）中位数、总生存期（OS）中位数、6个月PFS率、1年OS率和3/4级毒性。我们还比较了贝伐单抗与其他血管生成抑制剂之间的主要关注结果。所有分析均使用综合荟萃分析软件（2.0版）进行。
总共纳入842例患者进行分析：343例患者接受贝伐单抗治疗，386例接受其他血管生成抑制剂治疗，81例接受沙利度胺治疗。接受血管生成抑制剂治疗的复发性GBM患者的合并ORR、6个月PFS和1年OS分别为20.1%、19.5%和29.3%。与其他血管生成抑制剂相比，在复发性GBM中使用单药贝伐单抗显著提高了ORR和6个月PFS[相对危险度（RR）2.93，95%可信区间（CI）1.38 - 6.21；p = 0.025；RR 2.36，95%CI 1.46 - 3.82；p < 0.001]，而两组之间的1年OS无显著差异（p = 0.07）。与沙利度胺相比，复发性GBM中使用贝伐单抗治疗显著提高了ORR（RR 6.8，95%CI：2.64 - 17.6，p < 0.001），但6个月PFS（p = 0.07）和1年OS（p = 0.31）无改善。至于3/4级毒性，常见毒性为高血压，合并发生率为12.1%，而与血管生成抑制剂相关的高级别血栓栓塞事件（2.2%）、出血（5.1%）和胃肠道穿孔（2.8%）相对较低。
与其他血管生成抑制剂和沙利度胺相比，单药贝伐单抗作为复发性GBM患者的挽救治疗可提高ORR和6个月PFS，但不能提高1年OS。
