Abstract

Background

Standard treatment for glioblastoma is radiation with concomitant and adjuvant temozolomide for 6 cycles, although the optimal number of cycles of adjuvant temozolomide has long been a subject of debate. We performed a phase II randomized trial investigating whether extending adjuvant temozolomide for more than 6 cycles improved outcome.

Methods

Glioblastoma patients treated at 20 Spanish hospitals who had not progressed after 6 cycles of adjuvant temozolomide were centrally randomized to stop (control arm) or continue (experimental arm) temozolomide up to a total of 12 cycles at the same doses they were receiving in cycle 6. Patients were stratified by MGMT methylation and measurable disease. The primary endpoint was differences in 6-month progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and safety (Clinicaltrials.gov NCT02209948).

Results

From August 2014 to November 2018, 166 patients were screened, 7 of whom were ineligible. Seventy-nine patients were included in the stop arm and 80 in the experimental arm. All patients were included in the analyses of outcomes and of safety. There were no differences in 6-month PFS (control 55.7%; experimental 61.3%), PFS, or OS between arms. MGMT methylation and absence of measurable disease were independent factors of better outcome. Patients in the experimental arm had more lymphopenia (P < 0.001), thrombocytopenia (P < 0.001), and nausea and vomiting (P = 0.001).

Conclusions

Continuing temozolomide after 6 adjuvant cycles is associated with greater toxicity but confers no additional benefit in 6-month PFS.

Key Points

1. Extending adjuvant temozolomide to 12 cycles did not improve 6-month PFS.2. Extending adjuvant temozolomide did not improve PFS or OS in any patient subset.3. Extending adjuvant temozolomide was linked to increased toxicities.

中文翻译：

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一项 II 期随机、多中心、开放标签试验，在胶质母细胞瘤患者中继续辅助替莫唑胺超过六个周期 (GEINO 14-01)。

摘要

背景

胶质母细胞瘤的标准治疗是放疗，同时和辅助替莫唑胺共 6 个周期，尽管辅助替莫唑胺的最佳周期数长期以来一直是争论的主题。我们进行了一项 II 期随机试验，研究将替莫唑胺辅助治疗延长 6 个周期以上是否可以改善结果。

方法

在 20 家西班牙医院接受治疗且在 6 个周期的替莫唑胺辅助治疗后未进展的胶质母细胞瘤患者被集中随机分组，以停止（控制组）或继续（实验组）替莫唑胺，总共 12 个周期，剂量与他们在第 6 周期中接受的相同剂量. 患者按MGMT甲基化和可测量疾病进行分层。主要终点是 6 个月无进展生存期 (PFS) 的差异。次要终点是 PFS、总生存期 (OS) 和安全性 (Clinicaltrials.gov NCT02209948)。

结果

2014 年 8 月至 2018 年 11 月，共筛查 166 名患者，其中 7 人不合格。停止组包括 79 名患者，实验组包括 80 名患者。所有患者均被纳入结局和安全性分析。两组之间的 6 个月 PFS（对照 55.7%；实验 61.3%）、PFS 或 OS 没有差异。MGMT甲基化和没有可测量的疾病是更好结果的独立因素。实验组患者出现更多的淋巴细胞减少症（P  < 0.001）、血小板减少症（P  < 0.001）和恶心呕吐（P  = 0.001）。

结论

在 6 个辅助周期后继续使用替莫唑胺与更大的毒性相关，但在 6 个月的 PFS 中没有额外的益处。

关键点

1. 将替莫唑胺辅助治疗延长至 12 个周期并未改善 6 个月 PFS。2．延长替莫唑胺辅助治疗并未改善任何患者亚组的 PFS 或 OS。3．延长佐剂替莫唑胺与增加的毒性有关。