SURG-01. COMPLETE RESECTION IS NOT ASSOCIATED WITH IMPROVED SURVIVAL IN MGMT NON-METHYLATED GLIOBLASTOMA: RESULTS FROM THE GLARIUS TRIAL

Abstract

BACKGROUND: Although it is known that upfront complete surgical resection is associated with improved survival in glioblastoma, studies are lacking to confirm whether this holds true for the unfavorable patient population of O-6-methylguanine-DNA methyltransferase (MGMT) non-methylated glioblastoma. Here, we investigated the association of survival with the extent of resection in the GLARIUS study, a randomized phase II trial of bevacizumab/irinotecan (BEV/IRI) versus standard temozolomide (TMZ) in MGMT non-methylated glioblastoma. METHODS: Patients included in the modified intention-to-treat (ITT, n=170) population were stratified by extent of resection (partial vs. complete) as determined by early (>72h) postoperative contrast-enhanced MRI. In a Kaplan-Meier analysis, we compared overall survival (OS) between the groups in each treatment arm. A Cox regression analysis was used to detect whether complete resection was of prognostic value and independent of canonical prognostic markers, including age and Karnofsky performance score (KPS). RESULTS: In the BEV/IRI arm, 58 patients (50%) each underwent partial (PR) and complete resection (CR). In the TMZ arm, 29 patients (55%) underwent partial and 24 (45%) complete resection. Prognostic factors, including age and KPS, were balanced between patients with PR and CR. Neither in the BEV/IRI arm (CR, median OS [mOS], 17.3 [95% CI, 15.5-21.4] versus PR, mOS, 16.5 [95% CI, 14.9-17.9]; Hazard Ratio [HR], 0.79 [95% CI, 0.53-1.20]; p=0.28) nor in the TMZ arm (CR, mOS, 18.0 [95% CI, 17.1-21.3] versus PR, mOS, 15.3 [95% CI, 10.6-21.1]; HR, 0.77 [95% CI, 0.43-1.40]; p=0.40) patients with CR derived a significant OS benefit compared to those with PR. In a multivariable Cox regression analysis, this effect did not change after accounting for canonical prognostic markers. CONCLUSIONS: In the GLARIUS trial, patients with complete resection derived no relevant survival benefit as compared with partially resected patients. However, the small sample size, in the TMZ arm in particular, limits our analysis.