Neuro Oncol. 2017 Mar 24. doi: 10.1093/neuonc/nox025. [Epub ahead of print]

Blumenthal DT1, Gorlia T1, Gilbert MR1, Kim MM 1, Burt Nabors L1, Mason WP1, Hegi ME1, Zhang P1, Golfinopoulos V1, Perry JR1, Hyun Nam D1, Erridge SC1, Corn BW1, Mirimanoff RO1, Brown PD1, Baumert BG1, Mehta MP1, van den Bent MJ1, Reardon DA1, Weller M1, Stupp R1.

 

Author information:

1

    Tel-Aviv Sourasky Medical Center, Tel-Aviv University (D.T.B., B.W.C.); European Organization for Research and Treatment of Cancer, Brussels (EORTC) (D.T.B., T.G., V.G.); National Institutes of Health (M.R.M.); University of Alabama at Birmingham (L.B.N.); Princess Margaret Cancer Centre, University of Toronto (W.P.M.); Lausanne University Hospital (M.E.H., R.O.M., R.S.); NRG Oncology Statistics and Data Management Center (P.Z.); Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto (J.R.P.); Samsung Medical Center, Sungkyunkwan University School of Medicine (D.H.N.); Edinburgh Cancer Centre (S.C.E.); Mayo Clinic (P.D.B.); Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre (B.G.B.); Miami Cancer Institute (M.P.M.); Erasmus University Hospital (M.J.v.d.B.); Dana-Farber Cancer Institute and Harvard Medical School (D.A.R.); University of Zurich (M.W., R.S.).

 

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.

PMID: 28371907