Incorporating interferon alfa into standard care prolongs overall survival (OS) in patients with newly diagnosed, high grade glioma, according to research published in JAMA Network Open.
In a phase 3 trial, patients who received interferon alfa, temozolomide, and radiotherapy after surgery had longer OS than patients who received temozolomide and radiotherapy after surgery. There was no significant difference in progression-free survival (PFS) between the treatment arms.
This phase 3 trial (ClinicalTrials.gov Identifier: NCT01765088) enrolled 199 patients with newly diagnosed, high grade glioma from 15 medical centers in China. At baseline, the median age was 46.9 years, and 60.3% of patients were men.
Within 6 weeks after undergoing surgery, the patients were randomly assigned to the interferon alfa arm (n=100) or the standard care arm (n=99). Patients in both arms received concurrent radiotherapy (60 Gy) and temozolomide (75 mg/m2/day for 42 days).
After a 4-week period without treatment, patients in the interferon alfa arm received interferon alfa (3 million U on days 1, 3, and 5) plus temozolomide (150-200 mg/m2 on days 2-6) every 28 days. Patients in the standard care arm received temozolomide (150-200 mg/m2 on days 1-5) every 28 days. Both arms received a maximum of 12 cycles of treatment.
The median follow-up was 66.0 months. The median OS was significantly longer in the interferon alfa arm than in the standard care arm — 26.7 months and 18.8 months, respectively (hazard ratio [HR], 0.64; 95% CI, 0.47-0.88; P =.005).
The median 2-year OS rate was 57.4% in the interferon alfa arm and 37.3% in the standard care arm. The 5-year OS rates were 18.1% and 9.1%, respectively.
Among patients with unmethylated MGMT, the median OS was significantly longer with interferon alfa than with standard care — 24.7 months and 17.4 months, respectively (HR, 0.57; 95% CI, 0.37-0.87; P =.008). For patients with methylated MGMT, there was no significant difference in OS between the arms (HR, 0.77; 95% CI, 0.49-1.21; P =.25).
In the overall population, there was no significant difference in PFS between the arms. The median PFS was 14.8 months in the interferon alfa arm and 12.9 months in the standard care arm (HR, 0.79; 95% CI, 0.59-1.06; P =.11).
The 2-year PFS rate was 27.9% in the interferon alfa arm and 18.5% in the standard care arm. The 5-year PFS rates were 9.6% and 4.8%, respectively.
In the interferon alfa arm, the rate of grade 1 adverse events (AEs) was 2.0%, and the rate of grade 2 AEs was 5.0%. One patient (1.0%) had grade 3 influenza-like symptoms after the first cycle of interferon alfa plus temozolomide. This patient stopped treatment with interferon alfa but received temozolomide alone. There were no grade 4 AEs.
“In this randomized clinical trial, therapy consisting of temozolomide combined with interferon alfa prolonged the survival time of patients with newly diagnosed HGG [high grade glioma], especially those with MGMT unmethylated tumors, compared with the standard temozolomide regimen, and the toxic effects remained tolerable,” the researchers wrote. “Thus, we suggest that patients with MGMT unmethylated HGG receive temozolomide plus interferon alfa combination treatment.”
Guo C, Yang Q, Xu P, et al. Adjuvant temozolomide chemotherapy with or without interferon alfa among patients with newly diagnosed high-grade gliomas: A randomized clinical trial. JAMA Netw Open. Published online January 27, 2023. doi:10.1001/jamanetworkopen.2022.53285