Adding marizomib to standard treatment did not improve survival in patients with newly diagnosed glioblastoma, according to results of a phase 3 trial.
The results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Patrick Roth, MD, of University Hospital Zürich in Switzerland.
Dr Roth explained that marizomib — an irreversible proteasome inhibitor that crosses the blood-brain barrier — had previously demonstrated activity in phase 1/2 studies in patients with newly diagnosed or recurrent glioblastoma.
The phase 3 MIRAGE trial (ClinicalTrials.gov Identifier: NCT03345095) enrolled 749 adults with newly diagnosed glioblastoma who had undergone total resection, partial resection, or open biopsy.
All patients received standard treatment, consisting of involved-field radiotherapy with concomitant temozolomide as well as 6 cycles of maintenance with temozolomide. Patients in the experimental treatment arm received marizomib as well, both during radiotherapy and as part of maintenance.
At a preplanned interim analysis, there was no significant difference in median overall survival between the standard treatment arm and the marizomib arm — 15.90 months and 15.67 months, respectively (hazard ratio [HR], 1.00; 95% CI, 0.68-1.47; P =.9951).
Similarly, there was no significant difference in progression-free survival between the standard treatment arm and the marizomib arm — 6.14 months and 6.24 months, respectively (HR, 1.02; 95% CI, 0.81-1.28; P =.8694).
At least 1 serious treatment-related adverse event (AE) occurred in 13.4% of patients in the standard care arm and 24.9% of patients in the marizomib arm. Grade 3/4 treatment-related AEs occurred in 20.5% and 42.6%, respectively.
Central nervous system (CNS) AEs and psychiatric AEs were more common in the marizomib arm than in the standard treatment arm. The rate of CNS AEs was 66.6% and 27.9%, respectively, and the rate of psychiatric AEs was 52.1% and 6.4%, respectively.
The researchers are conducting further analyses of data from this trial, including stratifying survival data based on MGMT promoter methylation status.
Disclosures: This research was supported by Celgene, a subsidiary of Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Roth P, Gorlia T, Reijneveld JC, et al. EORTC 1709/CCTG CE.8: a phase III trial of marizomib in combination with temozolomide-based radiochemotherapy versus temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma. J Clin Oncol. 2021;39:(suppl 15; abstr 2004). doi:10.1200/JCO.2021.39.15_suppl.2004