by Dr. C.H. Weaver M.D. 6/2020
The immune checkpoint inhibitor Opdivo did not improve survival when used to treat recurrent Glioblastoma according to the results of the first large clinical trial comparing the novel immunotherapy to Avastin, a standard treatment for brain cancers. Analyses however did suggest certain patients may benefit from immunotherapy.
About Checkpoint Inhibitors
Opdivo (nivolumab) belongs to a class of medicines called “checkpoint inhibitors.” Checkpoint inhibitors are a novel precision cancer immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD-L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade detection and attack by certain immune cells in the body. A checkpoint inhibitor can block the PD-1 and PD-L1 pathway and enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the colon cancer cells.
The CheckMate 143 clinical trial evaluated whether Opdivo alone could improve survival in patients with recurrent glioblastoma compared with the antibody against vascular endothelial growth factor (VEGF) Avastin (bevacizumab). In the trial 184 patients received Opdivo and 185 received Avastin between September 2014 and May 2015.
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The study revealed that Avastin had a superior response rate and Opdivo did not delay cancer progression or prolong survival when used to treat recurrent glioblastoma. Average survival was ~ 10 for both Avastin and Opdivo treated patients. Additional analysis identified two factors associated with improved median survival (MGMT promoter methylation and lack of corticosteroid use). The authors reported that MGMT-methylated patients with no baseline steroid use experienced a trend toward improved survival (Opdivo 17 months compared to Avastin 10 months). patients with methylated MGMT promoter glioblastoma and no baseline corticosteroids may potentially derive benefit from immune checkpoint inhibition.2 This may be consistent with observations reported with Keytruda, another checkpoint inhibitor that appears promising in an initial report when used as neoadjuvant therapy before surgery.
- 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
- 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