Abstract
BACKGROUND: The course of glioblastoma (GBM) is worse in elderly and low KPS patients. The NORDIC and NOA08 clinical trials proved the non-inferiority of temozolomide (TMZ) treatment to radiotherapy alone for GBM MGMT promoter methylated (MGMT MET) elderly patients. TMZ alone is thus recommended in guidelines as first line of treatment for this group of patients. The data of real life efficacy of this treatment are sparse. MATERIAL AND METHODS: We retrospectively evaluated the data of GBM MGMT MET patients, older than 65y that were treated in the Neuro-oncology unit at Sheba MC during 2012-2022. The treatment was adjuvant TMZ 200mg/m2/day 5 days q28 days. We compared treatment outcomes in our patients to the results of the NORDIC and NOA08 RCTs. RESULTS: 36 patients were included in our analysis with stereotactic biopsy for diagnosis in 47% of them: 34 patients had GBM, 1 had WHO grade 3 Astrocytoma and in 1 patient the diagnosis was made by imaging (non diagnostic biopsy). Of this group, 25 were males and 11 females. The mean age was 76y (64-90) and 96% had KPS ≤ 60. Only one patient had IDH 1 mutation and in 9 cases IDH status was unknown. The interval from diagnosis to treatment was 2-19 weeks (median 6 weeks). The number of TMZ cycles was 1-12 (mean of 4 cycles after the exclusion of 11 patients who received less than 3 cycles). Median PFS/OS was 3 /7.5 months and 5/11 months respectively for the whole group and for patients that received ≥3 cycles. The 12/18/24 months survival rate was 33%/13%/8% respectively. 21 patients received second line treatment: 13 radiotherapy, 1 TMZ re-challenge and 7 Bevacizumab. Eight patients received a third line of treatment: 2 radiotherapy, 4 Bevacizumab, 1 Procarbazine and 1 TMZ. Grade 3-4 hematological toxicity was documented in 20% of the patients, with infections in 12.5% and bleeding in 4%. Fatigue was reported in 17% of the patients. CONCLUSION: While our patients were older and with lower KPS than the patients in the RCTs the efficacy of TMZ only treatment was comparable with the clinical trials results with mOS of 11/11.9/8.3 month in Sheba/NOA08/Nordic patients, PFS of 5/8.4/NA in Sheba/NOA08/Nordic patients respectively. The main toxicity reported in all 3 data sets was hematological 20%/38%/12% in Sheba/NOA08/Nordic patients. We can conclude that TMZ only for GBM MGMT MET elderly patients in real clinical set is a valuable and safe first line treatment.