title: Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG.
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.
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Deborah T
authors.initials: DT
authors.lastname: Blumenthal
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gorlia
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Kim
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: L
authors.initials: L
authors.lastname: Burt Nabors
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Warren P
authors.initials: WP
authors.lastname: Mason
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Monika E
authors.initials: ME
authors.lastname: Hegi
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Peixin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Golfinopoulos
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: James R
authors.initials: JR
authors.lastname: Perry
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Do
authors.initials: D
authors.lastname: Hyun Nam
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Sara C
authors.initials: SC
authors.lastname: Erridge
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Corn
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: René O
authors.initials: RO
authors.lastname: Mirimanoff
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Brigitta G
authors.initials: BG
authors.lastname: Baumert
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: van den Bent
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.affiliation: Tel-Aviv Sourasky Medical Center, Tel-Aviv University; European Organization for Research and Treatment of Cancer, Brussels (EORTC); National Institutes of Health (M.R.M.); University of Alabama at Birmingham; Princess Margaret Cancer Centre, University of Toronto; Lausanne University Hospital; NRG Oncology Statistics and Data Management Center; Odette Cancer Centre and Sunnybrook Health Sciences Centre, University of Toronto; Samsung Medical Center, Sungkyunkwan University School of Medicine; Edinburgh Cancer Centre; Mayo Clinic; Robert-Janker Clinic at the University of Bonn Medical Centre, and MAASTRO clinic, GROW School for Oncology, Maastricht University Medical Centre; Miami Cancer Institute; Erasmus University Hospital; Dana-Farber Cancer Institute and Harvard Medical School; University of Zurich.
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003131:Combined Modality Therapy / Q000379:methods; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000187:drug effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D000077204:Temozolomide
keywords: adjuvant; glioblastoma; maintenance; temozolomide; treatment duration