Temozolomide Bests Nivolumab in Glioblastoma With Unmethylated MGMT Promoter

Image of glioblastoma.
Image of glioblastoma.
Overall and progression-free survival were superior with temozolomide.

Temozolomide plus radiotherapy (RT) should remain the standard first-line treatment for glioblastoma, regardless of MGMT promoter status, according to researchers.

Results of a phase 3 trial showed better outcomes with temozolomide plus RT than with nivolumab plus RT in glioblastoma patients with unmethylated MGMT promoter. The results were published in Neuro-Oncology.

The phase 3 CheckMate 498 trial (ClinicalTrials.gov Identifier: NCT02617589) included 560 adults with previously untreated glioblastoma with unmethylated MGMT promoter. They were randomly assigned to receive nivolumab plus RT (n=280) or temozolomide plus RT (n=280). 

At baseline, the median age was 59.5 (range, 18-83) years in the nivolumab arm and 56.0 (range, 23-81) years in the temozolomide arm. A majority of patients were men (67.9% in the nivolumab arm and 62.5% in the temozolomide arm), had stage IV disease (78.2% and 72.1%, respectively), and underwent complete resection (53.9% vs 51.4%). 

The primary endpoint of overall survival (OS) was not met, as OS was longer in the temozolomide arm. The median OS was 13.4 months with nivolumab and 14.9 months with temozolomide (hazard ratio [HR], 1.31; 95% CI, 1.09-1.58; P =.0037). The 12 month OS rate was 58.3% and 62.3%, respectively. The 24-month OS rate was 10.3% and 21.2%, respectively.

Progression-free survival (PFS) was also longer with temozolomide. The median PFS was 6.0 months with nivolumab and 6.2 months with temozolomide (HR, 1.38; 95% CI, 1.15-1.65). The 12-month PFS rate was 5.7% and 17.7%, respectively. The 18-month OS rate was 3.0% and 8.1%, respectively.

The objective response rate was 7.8% with nivolumab and 7.2% with temozolomide.

Rates of treatment-related adverse events (TRAEs) were similar between the treatment arms. Any-grade TRAEs occurred in 72.7% of patients in the nivolumab arm and 75.6% of those in the temozolomide arm. Rates of grade 3-4 TRAEs were 21.9% and 25.1%, respectively.

TRAEs that occurred more frequently with temozolomide included lymphopenia, neutropenia, and thrombocytopenia. TRAEs that were more common with nivolumab included hypothyroidism, pyrexia, and rash. 

Treatment discontinuation due to TRAEs occurred in 8.6% of patients in the nivolumab arm and 5.8% of those in the temozolomide arm.

“Overall, our results indicate that immunotherapy with nivolumab is not a suitable replacement for chemotherapy with temozolomide, despite the chemoresistance of this difficult-to-treat population,” the researchers concluded.

Disclosures: This study was funded by 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.


Omuro A, Brandes AA, Carpentier AF, et al. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase 3 trial. Neuro Oncol. Published online April 14, 2022. doi:10.1093/neuonc/noac099

This article originally appeared on Cancer Therapy Advisor