ACT-8 A RANDOMIZED PHASE III STUDY OF HYPOFRACTIONATED RADIOTHERAPY COMBINED WITH TEMOZOLOMIDE IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA: JCOG1910 (AGEDGLIO-PIII)

Abstract

Abstract Background The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy (40 Gy in 15 fractions) with temozolomide. Further reduction of fractionation is expected to reduce the burden for elderly patients without decreasing therapeutic efficacy. Methods This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant and adjuvant temozolomide in terms of overall survival (OS) in elderly patients aged 71 or older with newly diagnosed glioblastoma. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. MGMT promoter methylation was included as an adjustment factor, and tumor specimen have been collected soon after the tumor resection and molecular diagnosis has been made centrally before randomization. A total of 270 patients will be accrued from 55 Japanese institutions in 4 years and follow-up will last 2 years. Results More than a half of patients (160 /270 cases) have been recruited between August 2020 and July 2022. Molecular diagnosis was made all but one cases, and diagnosis was made centrally within around 7 days after receiving the tumor specimen. There were one grade 4 severe adverse event and one treatment related death. Discussion Registration has been made smoothly without substantial delay due to central molecular diagnosis. The study has been safely performed for elderly patients. If the primary endpoint is met, hypofractionated radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma.