TY  - JOUR
AU  - Herrlinger, Ulrich
AU  - Tzaridis, Theophilos
AU  - Mack, Frederic
AU  - Steinbach, Joachim Peter
AU  - Schlegel, Uwe
AU  - Sabel, Michael
AU  - Hau, Peter
AU  - Kortmann, Rolf-Dieter
AU  - Krex, Dietmar
AU  - Grauer, Oliver
AU  - Goldbrunner, Roland
AU  - Schnell, Oliver
AU  - Bähr, Oliver
AU  - Uhl, Martin
AU  - Seidel, Clemens
AU  - Tabatabai, Ghazaleh
AU  - Kowalski, Thomas
AU  - Ringel, Florian
AU  - Schmidt-Graf, Friederike
AU  - Suchorska, Bogdana
AU  - Brehmer, Stefanie
AU  - Weyerbrock, Astrid
AU  - Renovanz, Miriam
AU  - Bullinger, Lars
AU  - Galldiks, Norbert
AU  - Vajkoczy, Peter
AU  - Misch, Martin
AU  - Vatter, Hartmut
AU  - Stuplich, Moritz
AU  - Schäfer, Niklas
AU  - Kebir, Sied
AU  - Weller, Johannes
AU  - Schaub, Christina
AU  - Stummer, Walter
AU  - Tonn, Jörg-Christian
AU  - Simon, Matthias
AU  - Keil, Vera C
AU  - Nelles, Michael
AU  - Urbach, Horst
AU  - Coenen, Martin
AU  - Wick, Wolfgang
AU  - Weller, Michael
AU  - Fimmers, Rolf
AU  - Schmid, Matthias
AU  - Hattingen, Elke
AU  - Pietsch, Torsten
AU  - Coch, Christoph
AU  - Glas, Martin
TI  - Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA–09): a randomised, open-label, phase 3 trial
JO  - The lancet 
VL  - 393
IS  - 10172
SN  - 0140-6736
CY  - London [u.a.]
PB  - Elsevier
M1  - FZJ-2019-01486
SP  - 678 - 688
PY  - 2019
AB  - BackgroundThere is an urgent need for more effective therapies for glioblastoma. Data from a previous unrandomised phase 2 trial suggested that lomustine-temozolomide plus radiotherapy might be superior to temozolomide chemoradiotherapy in newly diagnosed glioblastoma with methylation of the MGMT promoter. In the CeTeG/NOA-09 trial, we aimed to further investigate the effect of lomustine-temozolomide therapy in the setting of a randomised phase 3 trial.MethodsIn this open-label, randomised, phase 3 trial, we enrolled patients from 17 German university hospitals who were aged 18–70 years, with newly diagnosed glioblastoma with methylated MGMT promoter, and a Karnofsky Performance Score of 70% and higher. Patients were randomly assigned (1:1) with a predefined SAS-generated randomisation list to standard temozolomide chemoradiotherapy (75 mg/m2 per day concomitant to radiotherapy [59–60 Gy] followed by six courses of temozolomide 150–200 mg/m2 per day on the first 5 days of the 4-week course) or to up to six courses of lomustine (100 mg/m2 on day 1) plus temozolomide (100–200 mg/m2 per day on days 2–6 of the 6-week course) in addition to radiotherapy (59–60 Gy). Because of the different schedules, patients and physicians were not masked to treatment groups. The primary endpoint was overall survival in the modified intention-to-treat population, comprising all randomly assigned patients who started their allocated chemotherapy. The prespecified test for overall survival differences was a log-rank test stratified for centre and recursive partitioning analysis class. The trial is registered with ClinicalTrials.gov, number NCT01149109.FindingsBetween June 17, 2011, and April 8, 2014, 141 patients were randomly assigned to the treatment groups; 129 patients (63 in the temozolomide and 66 in the lomustine-temozolomide group) constituted the modified intention-to-treat population. Median overall survival was improved from 31·4 months (95% CI 27·7–47·1) with temozolomide to 48·1 months (32·6 months–not assessable) with lomustine-temozolomide (hazard ratio [HR] 0·60, 95% CI 0·35–1·03; p=0·0492 for log-rank analysis). A significant overall survival difference between groups was also found in a secondary analysis of the intention-to-treat population (n=141, HR 0·60, 95% CI 0·35–1·03; p=0·0432 for log-rank analysis). Adverse events of grade 3 or higher were observed in 32 (51%) of 63 patients in the temozolomide group and 39 (59%) of 66 patients in the lomustine-temozolomide group. There were no treatment-related deaths.InterpretationOur results suggest that lomustine-temozolomide chemotherapy might improve survival compared with temozolomide standard therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. The findings should be interpreted with caution, owing to the small size of the trial.
LB  - PUB:(DE-HGF)16
C6  - pmid:30782343
UR  - <Go to ISI:>//WOS:000458817300026
DO  - DOI:10.1016/S0140-6736(18)31791-4
UR  - https://juser.fz-juelich.de/record/860831
ER  -