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*, Thierry Gorlia, Mark R. Gilbert, Michelle M. Kim, L. Burt Nabors, Warren P. Mason, Monika E. Hegi, Peixin Zhang, Vassilis Golfinopoulos, James R. Perry, Do Hyun Nam, Sara C. Erridge, Benjamin W. Corn, René O. Mirimanoff, Paul D. Brown, Brigitta G. Baumert, Minesh P. Mehta, Martin J. Van Den Bent, David A. Reardon, Michael WellerRoger Stupp

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1119-1126
Number of pages8
JournalNeuro-oncology
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2017

Keywords

  • adjuvant
  • glioblastoma
  • maintenance
  • temozolomide
  • treatment duration

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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