Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial
Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial
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DOI：
10.1200/jco.2015.63.4691
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发表时间：
2016-05-10
影响因子：
45.3
通讯作者：
Glas, Martin
中科院分区：
文献类型：
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作者：
Herrlinger, Ulrich;Schaefer, Niklas;Glas, Martin
目的对于携带非甲基化 O-6-甲基鸟嘌呤-DNA 甲基转移酶启动子的新诊断胶质母细胞瘤患者，标准替莫唑胺 (TMZ) 充其量也具有有限的疗效。因此，GLARIUS 试验探索了贝伐珠单抗加伊立替康 (BEV+IRI) 作为 TMZ 的替代方案。 患者和方法 在该 II 期试验中，22 个中心的 182 名患者在非盲法试验中，在放疗 (RT) 期间被随机分配至 BEV（每 2 周 10mg/kg），随后维持 BEV（每 2 周 10mg/kg）加 IRI（每 2 周 125 mg/m(2)）。周）或在 RT 期间每日 TMZ（75 mg/m(2)），然后进行 6 个疗程的 TMZ（150-200 mg/m(2)/d，每 4 周 5 天）。主要终点是 6 个月后无进展生存率 (PFS-6)。 结果在改良意向治疗 (ITT) 人群中，PFS-6 从 TMZ 组的 42.6%（95% CI，29.4% 至 55.8%）增加到 BEV+IRI 组的 79.3%（95% CI，71.9% 至 86.7%；P < .001）。 PFS 从中位数 5.99 个月（95% CI，2.7 至 7.3 个月）延长至 9.7 个月（95% CI，8.7 至 10.8 个月；P < .001）。在疾病进展时，在 TMZ 组接受任何二线治疗的所有患者中，有 81.8% 接受了交叉 BEV 治疗。两组的总生存期 (OS) 无差异：BEV+IRI 组的中位 OS 为 16.6 个月（95% CI，15.4 至 18.4 个月），而 TMZ 组的中位 OS 为 17.5 个月（95% CI，15.1 至 20.5 个月）。欧洲癌症研究和治疗组织生活质量问卷 (QLQ)-C30 和 QLQ-BN20（包括认知功能）、卡诺夫斯基表现评分和简易精神状态检查评分的六个选定领域的生活质量 (QOL) 时程在治疗组之间没有差异。 结论与 TMZ 相比，BEV+IRI 的 PFS-6 率和中位 PFS 更高。然而，BEV+IRI 并没有改善操作系统，可能是因为交叉率高。与 TMZ 相比，BEV+IRI 没有改变 QOL。 (C) 2016 年美国临床肿瘤学会
PurposeIn patients with newly diagnosed glioblastoma that harbors a nonmethylated O-6-methylguanine-DNA methyltransferase promotor, standard temozolomide (TMZ) has, at best, limited efficacy. The GLARIUS trial thus explored bevacizumab plus irinotecan (BEV+IRI) as an alternative to TMZ.Patients and MethodsIn this phase II, unblinded trial 182 patients in 22 centers were randomly assigned 2: 1 to BEV (10mg/kg every 2 weeks) during radiotherapy (RT) followed by maintenance BEV (10mg/kg every 2 weeks) plus IRI(125 mg/m(2) every 2 weeks) or to daily TMZ (75 mg/m(2)) during RT followed by six courses of TMZ (150-200 mg/m(2)/d for 5 days every 4 weeks). The primary end point was the progression-free survival rate after 6 months (PFS-6).ResultsIn the modified intention-to-treat (ITT) population, PFS-6 was increased from 42.6% with TMZ(95% CI, 29.4% to 55.8%) to 79.3% with BEV+IRI (95% CI, 71.9% to 86.7%; P < .001). PFS was prolonged from a median of 5.99 months (95% CI, 2.7 to 7.3 months) to 9.7 months (95% CI, 8.7 to 10.8 months; P < .001). At progression, crossover BEV therapy was given to 81.8% of all patients who received any sort of second-line therapy in the TMZ arm. Overall survival (OS) was not different in the two arms: the median OS was 16.6 months (95% CI, 15.4 to 18.4 months) with BEV+IRI and was 17.5 months (95% CI, 15.1 to 20.5 months) with TMZ. The time course of quality of life (QOL) in six selected domains of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ)-C30 and QLQ-BN20 (which included cognitive functioning), of the Karnofsky performance score, and of the Mini Mental State Examination score was not different between the treatment arms.ConclusionBEV+IRI resulted in a superior PFS-6 rate and median PFS compared with TMZ. However, BEV+IRI did not improve OS, potentially because of the high crossover rate. BEV+IRI did not alter QOL compared with TMZ. (C) 2016 by American Society of Clinical Oncology