In a German phase III trial (CeTeG/NOA–09) reported in The Lancet, Herrlinger et al found that the addition of adjuvant lomustine to temozolomide and radiotherapy improved overall survival in newly diagnosed glioblastoma with methylated MGMT promoter. The researchers noted that findings should be viewed with caution due to the relatively small number of patients in the trial.
The open-label trial enrolled 141 patients from 17 sites in Germany between June 2011 and April 2014. Patients were randomly assigned to receive standard temozolomide chemoradiotherapy (75 mg/m² per day concomitant with radiotherapy at 59–60 Gy) followed by 6 courses of temozolomide at 150 to 200 mg/m² per day on the first 5 days of 4-week courses (n = 69), or up to 6 courses of lomustine at 100 mg/m² on day 1 plus temozolomide at 100 to 200 mg/m² per day on days 2 to 6 of 6-week courses in addition to radiotherapy at 59 to 60 Gy (n = 72).
The primary endpoint was overall survival in the modified intent-to-treat population. This group consisted of the 66 patients treated with lomustine/temozolomide and 63 patients treated with temozolomide who started allocated chemotherapy.
Survival and Adverse Events
The median overall survival was 48.1 months in the lomustine/temozolomide group vs 31.4 months in the temozolomide group (hazard ratio [HR] = 0.60, P = .0492). A secondary analysis in the full intention-to-treat population yielded a hazard ratio of 0.60 (P = .0432). Among 108 patients in the per-protocol population, median overall survival was 40.3 vs 30.4 months (HR = 0.53, P = .0453). In the modified intention-to-treat population, median progression-free survival was 16.7 vs 16.7 months (HR = 0.91, P = .4113).
In the modified intention-to-treat population, adverse events of grade ≥ 3 were observed in 59% of the lomustine/temozolomide group vs 51% of the temozolomide group. The most common adverse events in the lomustine/temozolomide group were thrombocytopenia (29% vs 24% in temozolomide group), leukopenia (15% vs 13%), neutropenia (12% vs 6%), and seizures (9% vs 6%). No treatment-related deaths were observed.
The investigators concluded, “Our 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.”
Ulrich Herrlinger, MD, of the Division of Clinical Neuro-oncology, University of Bonn Medical Center, is the corresponding author for The Lancet article.
Disclosure: The study was funded by the German Federal Ministry of Education and Research. The study authors' full disclosures can be found at thelancet.com.
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