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. 2017 Aug 1;19(8):1119-1126.
doi: 10.1093/neuonc/nox025.

Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG

Deborah T Blumenthal  1 , Thierry Gorlia  1 , Mark R Gilbert  1 , Michelle M Kim  1 , L Burt Nabors  1 , Warren P Mason  1 , Monika E Hegi  1 , Peixin Zhang  1 , Vassilis Golfinopoulos  1 , James R Perry  1 , Do Hyun Nam  1 , Sara C Erridge  1 , Benjamin W Corn  1 , René O Mirimanoff  1 , Paul D Brown  1 , Brigitta G Baumert  1 , Minesh P Mehta  1 , Martin J van den Bent  1 , David A Reardon  1 , Michael Weller  1 , Roger Stupp  1
Affiliations

Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG

Deborah T Blumenthal et al. Neuro Oncol. .

Abstract

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.

Keywords: adjuvant; glioblastoma; maintenance; temozolomide; treatment duration.

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Figures

Fig. 1
Fig. 1
(A, B) Overall and progression-free residual survival for patients treated with 6C vs >6C. Survival was calculated from start of cycle 6 + 28 days. Overall survival curves of the 6C vs >6C groups demonstrated no difference. Although median PFS was the same between the groups, 2-year PFS was superior for patients receiving >6C vs 6C. Adjusted P-values are displayed.
Fig. 2
Fig. 2
(A, B) Residual OS in MGMT methylated and unmethylated tumors. No difference in OS was seen among MGMT methylated or unmethylated patients receiving 6C vs >6C. Adjusted P-values are displayed.
See this image and copyright information in PMC

Comment in

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