Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O⁶-Methylguanine–DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial

Abstract

BEV+IRI resulted in a superior PFS-6 rate and median PFS compared with TMZ. However, BEV+IRI did not improve OS, potentially because of the high crossover rate. BEV+IRI did not alter QOL compared with TMZ.

Non-methylated MGMT as Predictive Factor in Newly Diagnosed Glioblastoma Multiforme Treated with Bevacizumab Concurrent with Radiotherapy Followed by Adjuvant Bevacizumab plus Irinotecan versus Temozolomide Concurrent with Radiotherapy Followed by Adjuvant Temozolomide

“…The prognostic factors with statically significance in correlating overall response with line of treatment were male sex (p-value=0.001), age less than or equal 50 yrs (p-value=0.001), performance status 0-1 (p-value= 0.003) and partial resection (p-value=0.001). As regard progression free survival was higher BEV+IRI versus TMZ 81.5%, 38.6% respectively which was statistically significant (p-value=0.00) and this was constant with that reported by Glarius study [15]. The PFS was prolonged by BEV was similar to that reported by the larger phase III AVAglio and RTOG 0825 trials [24] despite different line of treatment as patient received during radiotherapy.…”

“…In univariate analysis of overall survival with different prognostic factors, age, sex performance status and line of treatment were significant but in multivariate analysis, type of treatment was only statistically significant prognostic factor Grade 3 or higher adverse events were higher in the bevacizumab+IRI group than in TMZ group, this may be explained by higher incidence of hypertension in first group. However haematological toxicity was higher in TMZ group but nausea, vomiting and diarrhoea higher in BEV+IRI may be attributable to irinotecan side effect and this was constant with that reported by Glarius trial [15].…”

“…In univariate analysis with progression free survival, all prognostic factors including age, sex, performance status and treatment were statistically significant but in multivariate analysis, the prognostic factors with statistical significance were performance status, degree of resection and type of treatment. In our trial the progression free survival was translated into improvement in overall survival in contrast to as reported by Glarius [15], Aglio and RTOG 0825 trials in which improvement in PFS was not translated into improvement in overall survival [15,24]. The progression free survival was not translated into improvement in OS may be attributed to anti edema effect and pseudo progressive effect of BEV and not true anti neoplastic effect.…”

“…The most astonishing trial is Glarius trial which randomized 182 patients with glioblastome multiforme to bevacizumab concurrent with radiotherapy followed by sequential bevacizumab plus irinotecan bimonthly versus daily temozolomide concurrent radiotherapy then six cycles of temozolomide. It resulted in improvement in progression of survival not translated in improvement of overall survival [15]. Irinotecan has marginal activity in recurrent glioblastoma multiforme with progression free survival at 6 months 16% [16].…”

Bevacizumab as a last-line treatment for glioblastoma following failure of radiotherapy, temozolomide and lomustine

“…Bevacizumab has failed to prolong OS time when combined with radiotherapy and temozolomide chemotherapy as a first-line treatment, and at first recurrence when combined with lomustine (18)(19)(20)(21)26). Randomized clinical trials at second or further recurrences following the failure of radiotherapy, temozolomide and lomustine are lacking.…”