The first randomized phase 3 study to investigate an immune checkpoint inhibitor in patients with a primary brain tumor did not meet its primary endpoint of improved overall survival (OS), but the study may help to identify better treatment approaches. The results from the CheckMate 143 trial (ClinicalTrials.gov Identifier: NCT02017717), which were published in JAMA Oncology, investigated whether single-agent PD-1 blockade with nivolumab improved survival in patients with recurrent glioblastoma compared with the antibody against vascular endothelial growth factor (VEGF) bevacizumab.1

In this open-label trial, 184 patients received nivolumab and 185 received bevacizumab between September 2014 and May 2015. The median follow-up was 9.5 months and the study found that progression-free survival (PFS) rates and the overall response rate (ORR) were numerically better in the patients receiving bevacizumab. However, the durations of response were numerically longer in patients receiving nivolumab.

The median OS (mOS) was 9.8 months in the nivolumab group compared to 10.0 months in the bevacizumab (hazard ratio [HR], 1.04; 95% CI, 0.83-1.30), and the 12- month OS rate was 42% in both groups. There were no significant differences found in grade 3/4 treatment-related adverse events (TRAEs) between the 2 groups (nivolumab 18.1% vs bevacizumab 15.2%) and no new safety concerns were observed.

Related Articles

In an accompanying editorial, it was noted that even though the study did not meet its primary or secondary endpoints (PFS and ORR) for efficacy with nivolumab, some novel findings were revealed. In the analysis, there were 2 factors associated with improved median survival (MGMT promoter methylation and lack of corticosteroid use). The authors write that MGMT-methylated patients with no baseline steroid use experienced a trend toward improved survival (nivolumab 17.0 months vs bevacizumab 10.1 months), suggesting patients with methylated MGMT promoter glioblastoma and no baseline corticosteroids may potentially derive benefit from immune checkpoint inhibition.2


Continue Reading

References

  1. Reardon DA, Brandes AA, Omuro A, et al. Effect of nivolumab vs bevacizumab in patients with recurrent glioblastoma the CheckMate 143 phase 3 randomized clinical trial [published online May 21, 2020]. JAMA Oncol. doi: 10.1001/jamaoncol.2020.1024 
  2. Muftuoglu Y and Liau LM. Results from the CheckMate 143 clinical trial stalemate or new game strategy for glioblastoma immunotherapy? [Published online May 21, 2020] JAMA Oncol. doi: 10.1001/jamaoncol.2020.0857