Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG
Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG
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DOI：
10.1093/neuonc/nox025
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发表时间：
2017-08-01
期刊：
影响因子：
15.9
通讯作者：
Stupp, Roger
中科院分区：
文献类型：
--
作者：
Blumenthal, Deborah T.;Gorlia, Thierry;Stupp, Roger
背景：放疗同时辅以替莫唑胺(TMZ)是新诊断的胶质母细胞瘤(GBM)术后治疗的标准。该方案已被采用，但有不同的情况，包括将TMZ延长到6个周期以上。维持治疗的最佳持续时间仍然存在争议。方法：我们对新诊断的GBM的4个随机试验的个体患者数据进行了合并分析。纳入6周期后28天无进展的所有患者。继续TMZ的决定是根据当地的实践和标准，并由治疗医生自行决定。将患者分为治疗6个周期组和持续治疗6个周期以上组。根据年龄、功能状态、切除范围和MGMT甲基化进行调整，比较无进展和总存活率。结果：共有2214名GBM患者纳入4项试验。其中，624人符合分析条件，291人继续使用TMZ直到病情进展或最多12个周期，而333人在6个周期后停止使用TMZ。经预后因素调整后，服用TMZ超过6个周期的患者无进展存活率有所提高(风险比[HR]0.80[0.65-0.98]，P=0.03)，尤其是甲基化MGMT患者(n=342，HR 0.65[0.50-0.85]，P<；0.01)。然而，包括MGMT甲基化亚组在内的TMZ周期数(HR=0.92[0.71-1.19]，P=.52)并不影响总生存率(HR=0.89[0.63-1.26]，P=.51)。结论：持续TMZ周期超过6个周期并不能增加新诊断的GBM的总生存率。
Background: Radiation with concurrent and adjuvant (6 cycles) temozolomide (TMZ) is the established standard of postsurgical care for newly diagnosed glioblastoma (GBM). This regimen has been adopted with variations, including extending TMZ beyond 6 cycles. The optimal duration of maintenance therapy remains controversial.Methods: We performed pooled analysis of individual patient data from 4 randomized trials for newly diagnosed GBM. All patients who were progression free 28 days after cycle 6 were included. The decision to continue TMZ was per local practice and standards, and at the discretion of the treating physician. Patients were grouped into those treated with 6 cycles and those who continued beyond 6 cycles. Progression-free and overall survival were compared, adjusted by age, performance status, resection extent, and MGMT methylation.Results: A total of 2214 GBM patients were included in the 4 trials. Of these, 624 qualified for analysis 291 continued maintenance TMZ until progression or up to 12 cycles, while 333 discontinued TMZ after 6 cycles. Adjusted for prognostic factors, treatment with more than 6 cycles of TMZ was associated with a somewhat improved progression-free survival (hazard ratio [HR] 0.80 [0.65-0.98], P = .03), in particular for patients with methylated MGMT (n = 342, HR 0.65 [0.50-0.85], P < .01). However, overall survival was not affected by the number of TMZ cycles (HR = 0.92 [0.71-1.19], P = .52), including the MGMT methylated subgroup (HR = 0.89 [0.63-1.26], P = .51).Conclusions: Continuing TMZ beyond 6 cycles was not shown to increase overall survival for newly diagnosed GBM.