Concomitant radiotherapy plus temozolomide significantly increased progression-free survival versus radiotherapy alone in IDH-wildtype glioblastoma.
Treatment with concomitant radiotherapy plus temozolomide chemotherapy significantly increased progression-free survival (PFS) compared with radiotherapy alone in patients with IDH-wildtype glioblastoma, according to research from a retrospective study published in “Clinical Oncology”.
In the multi-center retrospective study, investigators evaluated 244 patients diagnosed with IDH-wildtype glioblastoma, of which, 67 patients (27.5%) received radiotherapy alone and 177 (72.5%) received concomitant radiotherapy with temozolomide chemotherapy. The mean PFS for all patients was 391.8 days (13.1 months); the standard deviation was 245.3 days ranging from a minimum of 51 days to a maximum of 96 months. However, when looking between treatment groups, these was also a statistically significant difference in PFS between the two.
Hazard ratio (HR): a statistical measure that compares the rate at which an event occurs in one group compared with another group over a period of time.
Progression-free survival (PFS): the time a patient lives without their disease spreading or worsening.
“In this cohort of Saudi patients with IDH-wildtype glioblastoma, concomitant radiotherapy with temozolomide chemotherapy added clinical benefit beyond that observed from radiotherapy alone, irrespective of MGMT-promoter methylation status,” lead study author, Dr. Maher Kurdi wrote in the report of data.
Kurdi is a Clinical Associate Professor and Chairman of the Department of Pathology at King Abdulaziz University, in Rabigh, Saudi Arabia.
Glioblastoma remains highly aggressive, with a median rate of survival between 9 to 15 months, for which, post-surgical radiotherapy has remained the standard-of-care treatment for decades, with various studies confirming its survival benefits. Furthermore, the role of chemotherapy, such as temozolomide, remains debated, as its efficacy depends largely on MGMT-promoter methylation. While temozolomide improves survival in some patients, conflicting data suggest it may not be effective in all cases. Based on this current unmet need in the patient population, researchers set out to conduct a retrospective multicenter study which evaluated the predictive impact of radiotherapy alone versus concurrent radiotherapy and temozolomide in patients with IDH-wildtype glioblastoma.
For the investigation, patients were selected from four hospitals in the western province of Saudi Arabia between 2013 and 2020 to be studied. Of these, 244 were considered eligible patients who were enrolled onto the study, all of whom were 18 years of age or older with newly diagnosed and histologically proven IDH-wildtype glioblastoma who had undergone complete surgical resection. Notably, the post-surgical treatment plan and the PFS were the only clinical data garnered for the study.
Patients were stratified based on IDH-wildtype, treatment modality and tumor recurrence time. Eligible participants either were treated with radiotherapy alone in group A or radiotherapy combined with temozolomide in group B after a complete surgical resection of the tumor and none of the patients included in the study received adjuvant therapies prior to their initial recurrence.
Regarding treatment dose, patients were treated with intensity-modulated radiation therapy using a standardized fraction radiation therapy regimen. For patients who received temozolomide, they were treated with a daily dose of 75 milligrams per square meter (mg/m2) every day throughout their radiotherapy course for a maximum of 49 days. Following a five-week interval, patients then received six cycles of adjuvant oral temozolomide at a dose ranging from 150 to 200 mg/m2 for five days every 28 days.
“There was a statistically significant difference in PFS between the two treatment groups,” Kurdi continued. “This indicates that patients receiving concomitant radiotherapy with temozolomide chemotherapy had a significantly longer PFS than those receiving radiotherapy alone, underscoring the efficacy of the combined treatment approach in managing glioblastoma post-surgically.
Investigators went on to share that the hazard ratio (HR) for PFS in patients treated with the combination versus radiotherapy alone was 0.48 in the univariable analysis, which indicate a significant benefit with the combined treatment regimen. In the multivariable analysis, this benefit was maintained with an HR of 0.5.
Age was noted as a significant factor in PFS, according to investigators, as each additional year of age increased the HR by 2% in the univariable analysis; with an HR of 1.01 in the multivariable analysis, the association remained significant. Based on these findings, older age is an independent predictor of shorter PFS in patients with glioblastoma.
“These results necessitate a new, adequately powered prospective clinical trial to investigate the effectiveness of combined treatment with temozolomide and other adjuvant therapies compared with radiotherapy alone in this specific patient population,” study authors concluded.
“Effects of Radiotherapy Alone Versus Concomitant Radiotherapy With Temozolomide Chemotherapy on the Outcome of IDH-wildtype Glioblastoma Patients” by Dr. Maher Kurdi, et al., Clinical Oncology.
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