Addition of interferon alfa to adjuvant temozolomide extends survival in high-grade glioma
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The addition of interferon alfa to temozolomide significantly extended survival among patients with newly diagnosed high-grade gliomas, according to data published in JAMA Network Open.
The temozolomide-interferon alfa combination also significantly prolonged median OS compared with temozolomide alone among patients with 06-methylguanine-DNA-methyltransferase (MGMT) unmethylation, researchers wrote.
“This randomized clinical trial confirmed an add-on effect of interferon alfa combined with temozolomide in high-grade glioma that is clinically significant, especially for those poorer-prognosis patients with MGMT-promoter unmethylated tumors,” Zhongping Chen, MD, PhD, of the department of neurosurgery and neuro-oncology at Sun Yat-Sen University Cancer Center in Guangzhou, China, told Healio.
Background
High-grade gliomas (HGGs) are the most common and aggressive type of primary brain tumor, with survival rates at 5 years of 30.9% for grade 3 gliomas and 6.6% for grade 4 gliomas.
Interferon alfa, which has been linked to innate immune system antiviral response and may interact with the blood-brain barrier, could enhance the benefits of temozolomide for patients with high-grade glioma, according to study background.
For that reason, researchers sought to compare the efficacy and safety of the combination vs. temozolomide alone among 199 patients aged 18 to 75 years (median age, 46.9 years; 60.3% men) with newly diagnosed high-grade glioma who had not received chemotherapy, radiotherapy or immunotherapy for their disease.
Methodology
The randomized, phase 3 clinical trial enrolled patients at 15 Chinese medical centers from May 1, 2012, to March 30, 2016.
Within 6 weeks after surgery, researchers randomly assigned patients temozolomide plus interferon alfa (n = 100) or standard treatment of temozolomide alone (n = 99). Patients then received standard radiotherapy concurrent with temozolomide at a dose of 75 mg/m2 for 42 days with standard fractionated radiotherapy.
Following a 4-week break, patients in the combined treatment group received up to 12 cycles of interferon alfa (3 million U on days 1, 3 and 5) plus temozolomide (150-200 mg/m2 on days 2-6) every 28 days, whereas patients in the standard treatment group received temozolomide alone (150-200 mg/m2 on days 1-5) every 28 days for a maximum of 12 cycles.
Two-year OS served as the primary endpoint, with secondary endpoints of 2-year PFS and treatment tolerability.
Median follow-up was 66 months (95% CI, 59.1-72.9).
Results
Researchers reported significantly longer median OS in the temozolomide-interferon alfa group compared with the standard group (26.7 months vs. 18.8 months; HR = 0.64; 95% CI, 0.47-0.88). The combination also significantly prolonged median OS in patients with MGMT unmethylation compared with temozolomide alone (24.7 months vs. 17.4 months; HR = 0.57; 95% CI, 0.37-0.87).
Results showed no significant difference in median PFS between the groups.
Seizure and influenza-like symptoms occurred more frequently in the combination group, with 2% of patients experiencing grade 1 toxic effects and 5% having grade 2 effects. One patient withdrew from the combination group after the first cycle due to grade 3 influenza-like symptoms, and then received temozolomide alone.
Next steps
Researchers hope to further analyze the effect of the combination treatment in future trials that include molecular profiling of tumors.
“We should initiate additional clinical trials to confirm the efficacy in patients with MGMT promoter unmethylated gliomas by molecular subgroup,” Chen told Healio.
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Guo C, et al. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2022.53285.
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