November 2024

NEUROSCIENCES

COMBINATION THERAPY DOES NOT EXTEND SURVIVAL IN GLIOBLASTOMA

Featuring: ​Priya Kumthekar, MD, ’11, ‘12 GME
Patients with a subtype of glioblastoma who received a combination treatment of a PARP inhibitor and standard chemotherapy did not demonstrate improved survival compared to chemotherapy and placebo, according to a recent clinical trial published in JAMA Oncology. 

Priya Kumthekar, MD, ’11, ‘12 GME, associate professor in the Ken and Ruth Davee Department of Neurology‘s Division of Neuro-oncology, was a coauthor of the study. 
 
Glioblastoma is the most common primary malignant brain tumor and currently has a five-year survival rate of only 6.9 percent, according to the National Brain Tumor Society. Despite standard therapy strategies, which includes surgery, radiation and temozolomide (a class of medication used to treat recurrent brain tumors), glioblastoma is extremely treatment-resistant, and the average length of survival is only eight months.  

​Approximately one-third of glioblastoma tumors express MGMT protein promoter methylation, an established biomarker that has been associated with how well a tumor will respond to chemotherapy treatments, such as temozolomide. Previous work has also demonstrated promising effects of the PARP inhibitor veliparib when combined with temozolomide in these patients.  

“Veliparib is in a category of drugs called a PARP inhibitor, which works by not allowing cancer cells to repair damaged DNA. When these damages build up in a cell, it can lead to cell death which is the goal of these types of drugs,” Kumthekar said. 

In the current clinical trial, a total of 447 patients diagnosed with glioblastoma with MGMT promoter hypermethylation who completed concomitant standard radiation and temozolomide were randomized to receive standard adjuvant temozolomide combined with either veliparib or placebo for six cycles. The average age for patients was 60 years and 42.5 percent of patients were female. 

“When glioblastoma is MGMT promoter-methylated, this means that it is more susceptible or more sensitive to the effects of alkylating chemotherapy, or in this case temozolomide. While patients who have tumors that are MGMT promoter-methylated fare better than those whose tumors do not possess this, the current treatment regimen remains a noncurative option,” said Kumthekar, who is also an associate professor of Medicine in the Division of Hematology and Oncology and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. 

​However, the investigators saw no significant difference in overall survival for patients who received temozolomide and veliparib compared to those who received temozolomide and placebo. The average overall survival was 24.8 months in the placebo group and 28.1 months for the veliparib group.  

“The trial results suggest that trends for enhanced survival in subsets of patients may provide insights for designing subsequent trials with the next generation of more selective, brain-penetrant PARP inhibitors,” the authors wrote.  

The work was supported by the National Cancer Institute grants U10CA180821, U10CA180882 and U24CA196171 (to the Alliance for Clinical Trials in Oncology); U10CA189812, UG1CA232760, UG1CA233329 and U10CA180868 (NRG Oncology); U10CA180888 (SWOG); and AbbVie.  
​This article was originally published in the Feinberg School of Medicine News Center on November 20, 2024. ​
Priya Kumthekar, MD, ’11, ‘12 GME, associate professor in the Ken and Ruth Davee Department of Neurology‘s Division of Neuro-oncology, was a coauthor of the study published in JAMA Oncology. ​

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