KEY TAKEAWAYS
- The phase III CheckMate 498 trial evaluated the efficacy of NIVO + RT compared with TMZ + RT.
- The trial’s primary aim was to determine the impact of NIVO + RT on OS in patients with GBM.
- The trial was a study that involved 560 patients who were randomized to receive either standard RT + NIVO or RT + TMZ.
- The trial outcome showed that TMZ + RT demonstrated a longer median OS than NIVO + RT.
- The safety profile of NIVO was consistent with previous studies, and no new safety signals were detected in this trial.
Previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter get modest benefits from the addition of temozolomide (TMZ) to radiotherapy (RT), which increases overall survival (OS) in patients with glioblastoma (GBM). The purpose of this phase III, open-label CheckMate 498 trial was to compare the effectiveness of nivolumab (NIVO) With RT to that of temozolomide (TMZ) + RT in patients with newly diagnosed GBM and an unmethylated MGMT promoter. Radiation therapy with either TMZ (75 mg/m2 daily during RT and 150-200 mg/m2/day 5/28 days during maintenance) or average RT (60 Gy) + NIVO (240 mg every 2 weeks for eight cycles, then 480 mg every 4 weeks) was randomized to patients 1:1. OS was the primary metric of success.
There were 560 patients randomized, 280 for each group. Compared to TMZ + RT, which had a hazard ratio (HR) of 1.31 (95% CI, 1.09-1.58; P =.0037) for the median overall survival (mOS) of 13.4 months, NIVO + RT had a mOS of 14.9 months (95% CI, 13.3-16.1). Progression-free survival was longer with NIVO + RT than TMZ + RT (HR, 1.38; 95% CI, 1.15 to 1.65): 6.0 months against 6.2 months (95% CI, 5.7 to 6.7). Comparing NIVO + RT and TMZ + RT, the response rates were 7.8% (9/116) and 7.2% (8/111), respectively; grade 3/4 TRAEs were 21.9% and 25.1%, and the rates of any-grade serious TRAEs were 17.3% and 7.6%. Even though TMZ + RT showed a longer mOS than NIVO + RT, the study did not reach its primary goal of enhanced OS. There were no unexpected safety signs found with NIVO. The findings of this study support TMZ + RT as the gold standard for treating GBM, as demonstrated by the differences between the treatment groups.
Source: https://pubmed.ncbi.nlm.nih.gov/35419607/
Clinical Trial : https://clinicaltrials.gov/ct2/show/NCT02617589
Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, Sumrall A, Baehring J, van den Bent M, Bähr O, Lombardi G, Mulholland P, Tabatabai G, Lassen U, Sepulveda JM, Khasraw M, Vauleon E, Muragaki Y, Di Giacomo AM, Butowski N, Roth P, Qian X, Fu AZ, Liu Y, Potter V, Chalamandaris AG, Tatsuoka K, Lim M, Weller M. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro Oncol. 2023 Jan 5;25(1):123-134. doi: 10.1093/neuonc/noac099. PMID: 35419607; PMCID: PMC9825306.
