MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive Glioblastoma: The DIRECTOR Trial

Clinical Cancer Research

Volumn 21, Issue 9, 2015, Pages 2057-2064

  Weller, Michael ^a   Tabatabai, Ghazaleh ^a   Kästner, Bärbel ^b   Felsberg, Jörg ^c   Steinbach, Joachim P ^d   Wick, Antje ^b   Schnell, Oliver ^e   Hau, Peter ^f   Herrlinger, Ulrich ^g   Sabel, Michael C ^c   Wirsching, Hans Georg ^a   Ketter, Ralf ^h   Bähr, Oliver ^d   Platten, Michael ^b   Tonn, Jörg C ^e   Schlegel, Uwe ⁱ   Marosi, Christine ^j   Goldbrunner, Roland ^k   Stupp, Roger ^l   Homicsko, Krisztian ^l   Pichler, Josef ^m   Nikkhah, Guido ⁿ   Meixensberger, Jürgen ^o   Vajkoczy, Peter ^p   Kollias, Spyros ^q   Hüsing, Johannes ^b   Reifenberger, Guido ^c   more..

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^c HEINRICH HEINE UNIVERSITY   (Germany)

^d UNIVERSITY HOSPITAL FRANKFURT   (Germany)

^e UNIVERSITY OF MUNICH   (Germany)

^f UNIVERSITY HOSPITAL REGENSBURG   (Germany)

^g UNIVERSITY HOSPITAL BONN   (Germany)

^h SAARLAND UNIVERSITY   (Germany)

ⁱ RUHR UNIVERSITY BOCHUM   (Germany)

^j MEDICAL UNIVERSITY OF VIENNA   (Austria)

^k UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^l LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^m KEPLER UNIVERSITY HOSPITAL   (Austria)

ⁿ UNIVERSITY OF FREIBURG   (Germany)

^o UNIVERSITY HOSPITAL LEIPZIG   (Germany)

^p CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^q UNIVERSITY HOSPITAL ZURICH   (Switzerland)

more..

Author keywords

[No Author keywords available]

Indexed keywords

METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; TEMOZOLOMIDE; ALKYLATING AGENT; DACARBAZINE; DNA LIGASE; DNA METHYLTRANSFERASE; MGMT PROTEIN, HUMAN; TUMOR MARKER; TUMOR SUPPRESSOR PROTEIN;

ADULT; AGE; ARTICLE; CANCER PROGNOSIS; CARDIOVASCULAR DISEASE; CHEMORADIOTHERAPY; CONTROLLED STUDY; DNA METHYLATION; DOSAGE SCHEDULE COMPARISON; DRUG DOSE INTENSIFICATION; DRUG RECHALLENGE; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; EARLY TERMINATION OF CLINICAL TRIAL; FEMALE; GASTROINTESTINAL DISEASE; GLIOBLASTOMA; HEMATOLOGIC DISEASE; HUMAN; HUMAN TISSUE; INFECTION; KARNOFSKY PERFORMANCE STATUS; LYMPHOCYTOPENIA; MAJOR CLINICAL STUDY; MALE; METABOLIC DISORDER; MINI MENTAL STATE EXAMINATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MUSCULOSKELETAL DISEASE; NEUROLOGIC DISEASE; NUCLEAR MAGNETIC RESONANCE IMAGING; OPEN STUDY; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROMOTER REGION; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY TRACT DISEASE; SALVAGE THERAPY; SKIN DISEASE; SURVIVAL RATE; WOUND INFECTION; ANALOGS AND DERIVATIVES; BRAIN NEOPLASMS; DISEASE FREE SURVIVAL; GENETICS; MIDDLE AGED; MORTALITY; PROGNOSIS; PROPORTIONAL HAZARDS MODEL; TUMOR RECURRENCE; YOUNG ADULT;

ADULT; ANTINEOPLASTIC AGENTS, ALKYLATING; BIOMARKERS, TUMOR; BRAIN NEOPLASMS; DACARBAZINE; DISEASE-FREE SURVIVAL; DNA METHYLATION; DNA MODIFICATION METHYLASES; DNA REPAIR ENZYMES; FEMALE; GLIOBLASTOMA; HUMANS; MALE; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; PROGNOSIS; PROMOTER REGIONS, GENETIC; PROPORTIONAL HAZARDS MODELS; TUMOR SUPPRESSOR PROTEINS; YOUNG ADULT;

EID: 84937939301     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-14-2737     Document Type: Article

References (38)

1. Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, et al. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 2014;15:e395-e403.
2. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-Temozolomide for newly diagnosed glioblastoma. N Engl J Med 2014;370:709-22.
3. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 2014;370:699-708.
4. Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): Amulticentre, randomised, open-label, phase 3 trial. Lancet Oncol 2014;15:1100-8.
5. Stupp R, Wong ET, Scott CB, Kirson ED, Palti Y, Taillibert S, et al. Interim analysis of the EF-14 trial: A prospective, multicenter trial of NovoTTF-100A together with temozolomide compared to temozolomide alone in patients with newly diagnosed GBM. [abstract]. In: Proceedings of the 19th Annual Meeting of the Society for Neuro-Oncology; November 13-16, 2014; Miami FL.
6. Weller M, Cloughesy T, Perry JR, Wick W. Standards of care for treatment of recurrent glioblastoma-Are we there yet? Neuro Oncol 2013;15:4-27.
7. Wick W, Puduvalli VK, Chamberlain MC, van den Bent MJ, Carpentier AF, Cher LM, et al. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol 2010;28: 1168-74.
8. Batchelor TT, Mulholland P, Neyns B, Nabors LB, Campone M, Wick A, et al. Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combinationwith lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol 2013;31:3212-8.
9. Wick W, Steinbach JP, Kuker WM, Dichgans J, Bamberg M, Weller M. One week on/one week off: A novel active regimen of temozolomide for recurrent glioblastoma. Neurology 2004;62:2113-5.
10. Brandes AA, Tosoni A, Cavallo G, Bertorelle R, Gioia V, Franceschi E, et al. Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neurooncologia (GICNO). Br J Cancer 2006;95:1155-60.
11. Perry JR, Belanger K, Mason WP, Fulton D, Kavan P, Easaw J, et al. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol 2010;28:2051-7.
12. Norden AD, Lesser GJ, Drappatz J, Ligon KL, Hammond SN, Lee EQ, et al. Phase 2 study of dose-intense temozolomide in recurrent glioblastoma. Neuro Oncol 2013;15:930-5.
13. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009;27:4733-40.
14. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, et al. Phase II trial of single-Agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2009;27:740-5.
15. Gerstner ER, McNamara MB, Norden AD, Lafrankie D, Wen PY. Effect of adding temozolomide to radiation therapy on the incidence of pseudoprogression. J Neurooncol 2009;94:97-101.
16. Brandsma D, van den BentMJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol 2009;22:633-8.
17. Felsberg J, Thon N, Eigenbrod S, Hentschel B, Sabel MC, WestphalM, et al. Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas. Int J Cancer 2011;129:659-70.
18. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114:97-109.
19. Felsberg J, Rapp M, Loeser S, Fimmers R, Stummer W, Goeppert M, et al. Prognostic significance of molecular markers and extent of resection in primary glioblastoma patients. Clin Cancer Res 2009;15:6683-93.
20. Weller M, Felsberg J, Hartmann C, Berger H, Steinbach JP, Schramm J, et al. Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: A prospective translational study of the German Glioma Network. J Clin Oncol 2009;27:5743-50.
21. Reifenberger G, Hentschel B, Felsberg J, Schackert G, Simon M, Schnell O, et al. Predictive impact ofMGMTpromoter methylation in glioblastoma of the elderly. Int J Cancer 2012;131:1342-50.
22. Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, et al. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: The NOA-08 randomised, phase 3 trial. Lancet Oncol 2012;13:707-15.
23. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 1975;31: 103-15.
24. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 1990;8:1277-80.
25. Wick A, Felsberg J, Steinbach JP, Herrlinger U, Platten M, Blaschke B, et al. Efficacy and tolerability of temozolomide in an alternatingweekly regimen in patients with recurrent glioma. J Clin Oncol 2007;25:3357-61.
26. Hasegawa T, Tango T. Permutation test following covariate-Adaptive randomization in randomized controlled trials. J Biopharm Stat 2009;19: 106-19.
27. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005;352:997-1003.
28. Weller M, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol 2010;6:39-51.
29. Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, et al. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 2009;27:5874-80.
30. van den BentMJ, Dubbink HJ, Sanson M, van der Lee-Haarloo CR, Hegi M, Jeuken JW, et al. MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: A report from EORTC Brain Tumor Group Study 26951. J Clin Oncol 2009;27:5881-6.
31. Bady P, Sciuscio D, Diserens AC, Bloch J, van den Bent MJ, Marosi C, et al. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status. Acta Neuropathol 2012;124: 547-60.
32. Wick W, Meisner C, Hentschel B, Platten M, Schilling A, Wiestler B, et al. Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation. Neurology 2013;81:1515-22.
33. Tolcher AW, Gerson SL, Denis L, Geyer C, Hammond LA, Patnaik A, et al. Marked inactivation of O6-Alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 2003;88: 1004-11.
34. Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA, et al. Dosedense temozolomide for newly diagnosed glioblastoma: A randomized phase III clinical trial. J Clin Oncol 2013;31:4085-91.
35. Brada M, Stenning S, Gabe R, Thompson LC, Levy D, Rampling R, et al. Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. J Clin Oncol 2010;28:4601-8.
36. Han SJ, Rolston JD, Molinaro AM, Clarke JL, Prados MD, Chang SM, et al. Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma. Neuro Oncol 2014;16:1255-62.
37. Wick A, Pascher C, Wick W, Jauch T, Weller M, Bogdahn U, et al. Rechallenge with temozolomide in patients with recurrent gliomas. J Neurol 2009;256:734-41.
38. Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, et al. Single-Agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): A randomised controlled phase 2 trial. Lancet Oncol 2014;15:943-53.